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Recent studies have suggested that textural characteristics of the intima-media complex (IMC) may be more useful than the intima-media thickness (IMT) in evaluating cardiovascular risk. The primary aim of our study was to investigate the association between texture features of the common carotid IMC and prevalent clinical cardiovascular disease (CVD). The secondary aim was to determine whether IMT and IMC texture features vary between the left and right carotid arteries. The study was performed on 2208 longitudinal-section ultrasound images of the left (L) and right (R) common carotid artery (CCA), acquired from 569 men and 535 women out of which 125 had clinical CVD. L and R sides of the IMC were intensity normalized and despeckled. The IMC was semiautomatically delineated for all images using a semiautomated segmentation system, and 61 different texture features were extracted. The corresponding IMT semiautomated measurements (mean±SD) of the L and R sides were 0.73±0.21 mm/0.69±0.19 mm for the normal population and 0.83±0.17 mm/0.79±0.18 mm for those with CVD. IMC texture features did not differ between the right- and left-hand sides. Several texture features were independent predictors of the presence of CVD. The multivariate logistic regression analysis combining age, IMT, and texture features produced a receiver operating characteristic curve with an area under the curve of 89%. A correct classification rate of 77% for separating the normal subject (NOR) versus CVD subjects was achieved using the support vector machine classifier with a combination of clinical features, IMT, and extracted texture features. Texture features provide additional information on the presence of clinical CVD, which is over and above that provided by conventional risk factors or IMT alone. The value of IMC texture features in the prediction of future cardiovascular events should be tested in prospective studies.

Objective Dynamic image analysis of carotid plaques has demonstrated that during systole and early diastole, all plaque components will move in the same direction (concordant motion) in some plaques. However, in others, different parts of the plaque will move in different directions (discordant motion). The aim of our study was (1) to determine the prevalence of discordant motion in symptomatic and asymptomatic plaques, (2) to develop a measurement of the severity of discordant motion, and (3) to determine the correlation between the severity of discordant motion and symptom prevalence. Methods A total of 200 patients with 204 plaques resulting in 50% to 99% stenosis (112 asymptomatic and 92 symptomatic plaques) had video recordings available of the plaque motion during 10 cardiac cycles. Video tracking was performed using Farneback's method, which relies on frame comparisons. In our study, these were performed at 0.1-second intervals. The maximum angular spread (MAS) of the motion vectors at 10-pixel intervals in the plaque area was measured in degrees. Plaques were classified as concordant (MAS, 120°). Results Motion was discordant in 89.1% of the symptomatic plaques but only in 17.9% of asymptomatic plaques (P < .001). The prevalence of symptoms increased with increasing MAS. For a MAS >120°, the hazard ratio for the presence of symptoms was 47.7 (95% confidence interval, 18.1-125.6) compared with the rest of the plaques after adjustment for the degree of stenosis and mean pixel motion. The area under the receiver operating characteristic curve for the prediction of the presence of symptoms using the MAS was 0.876 (95% confidence interval, 0.823-0.929). The use of the median MAS (120°) as a cutoff point classified 86% of the plaques correctly (sensitivity, 81.4%; specificity, 91.2%; positive predictive value, 90.2%; and negative predictive value, 83.0%). Conclusions The use of the MAS value to identify asymptomatic plaques at increased risk of developing symptoms and, in particular, stroke should be tested in prospective studies.

Objectives Patients with SLE have an increased risk of developing cardiovascular disease (CVD). Multiple studies have shown that these patients have increased numbers of carotid plaques and greater intima-media thickness (IMT) than healthy controls. Measures such as total plaque area (TPA) and plaque echogenicity may be more sensitive and more relevant to cardiovascular risk than presence of plaque and IMT alone. Our objective was to produce the first report of TPA and echogenicity in a population of patients with SLE. Methods One hundred patients with SLE and no history of clinical CVD were recruited. Clinical, serological and treatment variables were recorded and serum was tested for antibodies to apolipoprotein A-1 and high-density lipoprotein. Both carotid and both femoral artery bifurcations of each patient were scanned to determine IMT, TPA and echogenicity of plaques. Univariable and multivariable statistical analyses were carried out to define factors associated with each of these outcomes. Results Thirty-six patients had carotid and/or femoral plaque. Increasing age was associated with presence of plaque and increased IMT. Triglyceride levels were associated with presence of plaque. Mean (s.d.) TPA was 60.8 (41.6) mm2. Patients taking prednisolone had higher TPA. Most plaques were echolucent, but increased echogenicity was associated with prednisolone therapy and persistent disease activity. Conclusion TPA and plaque echogenicity in patients with SLE are associated with different factors than those associated with presence of plaque and IMT. Longitudinal studies may show whether these outcome measures add value in the management of cardiovascular risk in SLE.

Objective: Patients with systemic lupus erythematosus (SLE) have an increased risk of developing cardiovascular disease. Standard serum lipid measurements in clinical practice do not predict cardiovascular disease risk in patients with SLE. More detailed analysis of lipoprotein taxonomy could identify better predictors of cardiovascular disease risk in SLE. Approach and Results: Eighty women with SLE and no history of cardiovascular disease underwent carotid and femoral ultrasound scans; 30 had atherosclerosis plaques (patients with SLE with subclinical plaque) and 50 had no plaques (patients with SLE with no subclinical plaque). Serum samples obtained at the time of the scan were analyzed using a lipoprotein-focused metabolomics platform assessing 228 metabolites by nuclear magnetic resonance spectroscopy. Data were analyzed using logistic regression and 5 binary classification models with 10-fold cross validation. Patients with SLE had global changes in complex lipoprotein profiles compared with healthy controls despite having clinical serum lipid levels within normal ranges. In the SLE cohort, univariate logistic regression identified 4 metabolites associated with subclinical plaque; 3 subclasses of VLDL (very low-density lipoprotein; free cholesterol in medium and large VLDL particles and phospholipids in chylomicrons and extremely large VLDL particles) and leucine. Together with age, these metabolites were also within the top features identified by the lasso logistic regression (with and without interactions) and random forest machine learning models. Logistic regression with interactions differentiated between patients with SLE with subclinical plaque and patients with SLE with no subclinical plaque groups with the greatest accuracy (0.800). Notably, free cholesterol in large VLDL particles and age differentiated between patients with SLE with subclinical plaque and patients with SLE with no subclinical plaque in all models. Conclusions: Serum metabolites are promising biomarkers to uncover and predict multimetabolic phenotypes of subclinical atherosclerosis in SLE.

In recent years, it has become apparent that the severity of an asymptomatic carotid stenosis is not sufficient to assess the risk of stroke. Although the risk of stroke increases with increasing grades of stenosis, and as a result a stenosis of ≥80% is used by many surgeons as an indication for surgery, this subgroup does not contain the majority of strokes that will subsequently occur. In addition, because the severity of stenosis cannot identify subgroups with stroke risk higher than 2.5%, a very large number of operations (approximately 90) with an asymptomatic stenosis of ≥80% would need to undergo carotid endarterectomy to prevent one stroke for one year of follow-up.

BackgroundPatients with systemic lupus erythematosus (SLE) have an increased risk of developing cardiovascular disease (CVD) and 30-40% have sub-clinical atherosclerosis on vascular ultrasound scanning. Standard measurements of serum lipids in clinical practice do not predict CVD risk in patients with SLE. We hypothesise that more detailed analysis of lipoprotein taxonomy could identify better predictors of CVD risk in SLE.MethodsEighty patients with SLE and no history of CVD underwent carotid and femoral ultrasound scans; 30 had atherosclerosis plaques (SLE-P) and 50 had no plaques (SLE-NP). Serum samples obtained at the time of the scan were analysed using a lipoprotein-focused metabolomics platform assessing 228 metabolites by nuclear magnetic resonance spectroscopy. Data was analysed using logistic regression and five binary classification models with 10-fold cross validation; decision tree, random forest, support vector machine and lasso (Least Absolute Shrinkage and Selection Operator) logistic regression with and without interactions.ResultsUnivariate logistic regression identified four metabolites associated with the presence of sub-clinical plaque; three subclasses of very low density lipoprotein (VLDL) (percentage of free cholesterol in medium and large VLDL particles and percentage of phospholipids in chylomicrons and extremely large VLDL particles) and Leucine. Together with age, these metabolites were also within the top features identified by the lasso logistic regression (with and without interactions) and random forest machine learning models. Logistic regression with interactions differentiated between SLE-P and SLE-NP with greatest accuracy (0.800). Notably, percentage of free cholesterol in large VLDL particles and age were identified by all models as being important to differentiate between SLE-P and SLE-NP patients.ConclusionSerum metabolites are a promising biomarker for prediction of sub-clinical atherosclerosis development in SLE patients and could provide novel insight into mechanisms of early atherosclerosis development.

Background Patients with SLE have 5-10-fold increased risk of developing CVD compared to age and sex-matched controls. The average age of developing a first CVD event in patients with SLE is only 49. In this study we aimed to describe the rate and determinants of carotid plaque progression in a cohort of SLE patients who were asymptomatic of CVD at baseline. Methods We carried out vascular ultrasound studies of 100 patients with SLE asymptomatic of CVD at baseline. Sixty-nine patients were rescanned over a median of 5 years of follow up. Ninety-four percent who were re-scanned were women and the mean overall age was 46 years (SD 11). Clinical and CVD risk was assessed at baseline and follow up. The same protocol for assessment at baseline using B-mode Doppler ultrasound to measure intimal media thickness and plaque was used at follow up to assess progression. We also assessed total plaque area (TPA), a more sensitive measure of plaque, and echolucency expressed as gray scale median (GSM) which is linked to plaque lipid content. Results Of the 100 patients with a baseline scan, 69 patients had a second scan at a median of 5 years follow up. New plaque developed in 9% and 26% had an increase in plaque number. The mean overall IMT (0.111 vs 0.064, p < 0.01) and common carotid IMT (0.065 vs 0.055, p < 0.01) were significantly raised in plaque vs non-plaque patients. In a multi -variable analysis CIMT at follow-up was independently associated with age (beta 0.415, p < 0.001) and diastolic blood pressure (beta 0.285, p < 0.021). Independent predictors of plaque at follow-up scan on multi-variable analysis were age at scan>52 years (OR 10.41, CI 2.66-40.80) and systolic BP > 133 (OR 5.26, CI 1.396 - 19.862). In contrast, total cholesterol was negatively correlated with TPA (beta = -1.167, p = 0.002) and with GSM (beta = -0.513, p = 0.012). Conclusion Amongst these 69 patients, 26% had increased plaque and none had decreased plaque over a median of five years follow-up. Measurement of novel ultrasound variables such as TPA and echolucency may identify more modifiable risk factors that can be used to improve CVD outcomes in patients with SLE. Disclosures J. Bakshi: None. M. Griffin: None. S. Croca: None. F. Farhina: None. D. Isenberg: None. A. Nicolaides: None. A. Rahman: None.

Background Cardiovascular disease is a significant burden on SLE patients, and no satisfactory markers exist to predict atherosclerotic development in patients. This study utilised an orthogonal approach to develop a marker of cardiovascular progression with predictive value in SLE patients. Methods The earliest available sample from a cohort of 92 SLE patients was tested for anti-Domain I (aDI), anti Beta-2-Glycoprotein-I, and anti-Cardiolipin antibodies. Persistent positivity was not assessed. These patients then had vascular ultrasound scans (carotid and femoral arteries) (mean 10 years later) to assess subclinical atherosclerotic plaque. A range of demographic, clinical and serological markers were recorded at the time of the scan. Predictors of plaque presence were investigated using binary logistic regression. Results A total of 34 patients from the cohort of 92 had atherosclerotic plaque (37%). A total of 32 patients had aDI positivity, of which 20 (62.5%) also had Plaque, this is reflected by the significantly higher levels of aDI antibodies seen in Plaque patients (p < 0.01). Anti-DI positivity was predictive of the development of plaque in the future (Odds Ratio (OR) 5.476, p < 0.001). No association was seen for any other antibody tested. Multiple binary logistic regression showed aDI positivity had as much predictive value as triglyceride levels on the day of the scan (OR 3.5 vs 3.9, Table 1) for predicting plaque in patients. Age at scan was a third independent variable associated with atherogenic plaque. Conclusion Early aDI positivity may be a good marker of atherogenesis in SLE patients in the long term. Disclosures T.C.R. McDonnell: Other; I am an inventor on the patent for Domain I. F. Farinha: None. C. Pericleous: Other; This Author is an Inventor on the Patent for Domain I. M. Griffin: None. A. Nicolaides: None. S. Croca: None. I. Giles: Other; This Author is an Inventor on the Domain I Patent. A. Rahman: Other; This Author is an Inventor on the Domain I Patent..

Background Cardiovascular disease is a significant burden on SLE patients and no satisfactory markers exist to predict atherosclerotic development in patients. This study utilised an orthogonal approach to develop a marker of cardiovascular progression with predictive value in SLE patients. Methods The earliest available sample from a cohort of 92 SLE patients was tested for anti-Domain I (aDI), anti Beta-2-Glycoprotein-I, and anti-Cardiolipin antibodies. Persistent positivity was not assessed. These patients then had vascular ultrasound scans (carotid and femoral arteries) (mean 10 years later) to assess subclinical atherosclerotic plaque. A range of demographic, clinical and serological markers were recorded at the time of the scan. Predictors of plaque presence were investigated using binary logistic regression. Results A total of 34 patients from the cohort of 92 had atherosclerotic plaque (37%). A total of 32 patients had aDI positivity, of which 20 (62.5%) also had Plaque, this is reflected by the significantly higher levels of aDI antibodies seen in Plaque patients (p Conclusions Early aDI positivity may be a good marker of atherogenesis in SLE patients in the long term.

Background SLE patients have 5–10-fold increased risk of developing CVD compared to controls.1,2 In this study we aimed to describe the rate and determinants of carotid plaque progression in a cohort of SLE patients who were asymptomatic of CVD at baseline. Methods Vascular ultrasound studies of 100 patients with SLE asymptomatic of CVD was carried out at baseline. Sixty-nine patients were rescanned (94% female, mean overall age 46 years (SD 11)) over a median of 5 years of follow up. Clinical and CVD risk was assessed at baseline and follow up. B-mode Doppler ultrasound was used to measure intimal media thickness and plaque to assess progression. Total plaque area (TPA), a more sensitive measure of plaque, and echolucency expressed as gray scale median (GSM), linked to plaque lipid content were assessed. Results Of the 100 patients with a baseline scan, 69 patients had a second scan at a median of 5 years follow up. New plaque developed in 9% and 26% had an increase in plaque number. The mean overall IMT (0.111 vs 0.064, p 52 years (OR 10.41, CI 2.66–40.80) and systolic BP>133 (OR 5.26, CI 1.396 – 19.862). In contrast, total cholesterol was negatively correlated with TPA (beta =-1.167, p=0.002) and with GSM (beta =-0.513, p=0.012). Conclusions Amongst these 69 patients, 26% had progression and none had decreased plaque over a median of five years follow-up. Measurement of novel ultrasound variables such as TPA and echolucency may identify more modifiable risk factors that can be used to improve CVD outcomes in patients with SLE. Acknowledgements Rosetrees Trust References Bruce IN. ‘Not only...but also’: factors that contribute to accelerated atherosclerosis and premature coronary heart disease in systemic lupus erythematosus. Rheumatology(Oxford, England) 2005;44(12);1492–502. Manzi S, Meilahn EN, Rairie JE, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol 1997;145(5);408–15.

Through this study we are presenting the initial steps towards a real time motion analysis system to predict the stability of carotid bifurcation plaques. The analysis is performed on B-mode video loops. Loops are analyzed in order to follow systole and diastole sections of the cardiac cycle and trace the motion of plaques during these periods. We had created a system that applies Farnebacks optical flow estimation method in order to estimate the flow between consecutive frames or frames at a predefined interval. Over each pair of video frames we measure velocities, orientation and magnitude of movement. The goal is to identify if a plaque has movement spread to different angles or at nearby angles. This can help us identify discordant or concordant movement. In order to verify our system we had created a set of simulated videos that have structures moving in a similar way as done in a cardiac cycle and videos that move and appear as an atherosclerotic artery. Following these tests the system has been tested and results are presented on two carotid plaques videos classified visually as having concordant and discordant plaque movement.

We aimed to test the association between matrix metalloproteinase ( MMP) genetic polymorphisms and (a) intima–media thickness in the common carotid (IMTcc) and (b) the presence of plaques in the carotid and femoral bifurcations. Carotid and femoral bifurcations were scanned with ultrasound in 762 Cypriot community dwellers (46% men) over the age of 40 years. IMTcc and the presence of plaques were recorded. The MMP1 1G/2G, MMP3 5A/6A, MMP7 -181A>G, MMP9 R279Q, and MMP12 -82A>G polymorphisms were determined with the TaqMan method. In men, the presence of plaques in any bifurcation was associated with the MMP9 279Q allele (ORadjusted=4.50; 95% CI=2.0 to 10.1; padjusted=2.61; 95% CI=1.36 to 4.99; p=0.004). In women, the presence of femoral plaques was associated with the MMP12 -82G allele (ORadjusted=1.9; 95% CI=1.14 to 3.16; p=0.014). Our results suggest that the effect of common MMP genotypes on plaque presence may be site- and sex-dependent.

Accelerated atherosclerosis is a complication of the autoimmune rheumatic disease systemic lupus erythematosus (SLE). We questioned the role played by invariant natural killer T (iNKT) cells in this process because they not only are defective in autoimmunity but also promote atherosclerosis in response to CD1d-mediated lipid antigen presentation. iNKT cells from SLE patients with asymptomatic plaque (SLE-P) had increased proliferation and interleukin-4 production compared with those from SLE patients with no plaque. The anti-inflammatory iNKT cell phenotype was associated with dyslipidemia and was driven by altered monocyte phospholipid expression and CD1d-mediated cross-talk between iNKT cells and monocytes but not B cells. Healthy iNKT cells differentiated in the presence of healthy monocytes and SLE-P serum polarized macrophages toward an anti-inflammatory M2 phenotype. Conversely, patients with clinical cardiovascular disease had unresponsive iNKT cells and increased proinflammatory monocytes. iNKT cell function could link immune responses, lipids, and cardiovascular disease in SLE patients and, together with serum lipid taxonomy, help predict preclinical atherosclerosis in SLE patients.

Introduction Emerging data suggests that 3-dimensional (D) ultrasound (US) may provide us with a new tool for the identification of the vulnerable carotid plaque. Methods A systematic review of the PubMed, Scopus and Cochrane databases regarding the reproducibility and effectiveness of 3D US in evaluation of carotid plaque disease (CPD) was performed. Results Seven studies on the reproducibility of 3D ultrasound evaluation of plaque volume (PV) were identified. All studies reported good intra- and inter-observer reproducibility ranging from 2.8–6.0% to 4.2–7.6%, respectively. In addition, ten studies evaluating 3D carotid plaque progression with and without treatment were retrieved. In the 4 studies where 2D and 3D US features were compared, PV rather than intima media thickness (IMT) was a more sensitive marker of plaque change as a response to treatment. However, there were no studies evaluating changes in plaque morphology or specific composition features post-treatment with both 2 and 3D US. Finally, only one study was identified regarding the 3D composition differences of CPD between symptomatic and asymptomatic patients. Conclusion The current evidence supports the good reproducibility of the 3D US on the evaluation of carotid plaque volume, however with high heterogeneity between studies. There is also preliminary evidence that PV measurements may be more sensitive than IMT in the identification of plaque change post-treatment, though, more plaque-related evidence is necessary. Further research is needed to establish if 3D is superior to 2D US in the identification of the vulnerable carotid plaque in clinical settings.

Purpose. Visual carotid plaque classification on duplex imaging is moderately reproducible, and, although the literature is controversial, research to analyze and overcome this problem remains scarce. The aim of this study was to assess the effect of computer screen brightness on the intraobserver variation of visual plaque classification. Methods. One hundred asymptomatic noncalcified carotid plaques causing carotid stenosis >40% on duplex scanning, in 84 patients, were transferred to a personal computer, normalized, and classified into four groups of increasing echogenicity (types 1–4) at 50% and 100% of maximum monitor brightness settings. Baseline intraobserver variability of visual plaque classification at maximum brightness was also assessed. Results. Baseline intraobserver variability was moderate (Cohen's Kappa value 0.59, p < 0.001). Reduction in monitor brightness caused a systemic shift in echogenicity, with 51% of the type 2–4 plaques being classified as more echolucent. Likewise, Cohen's Kappa value decreased to 0.37, indicating poor agreement between the two classification rounds. Conclusion. Reduction in computer screen brightness deteriorates the intraobserver variation of visual plaque classification. This finding could explain some of the discrepancy in reproducibility results reported and should be taken into account when using visual characterization methods. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound, 2011

Background: Severity of stenosis remains the main factor for assessing risk of stroke in patients with internal carotid artery (ICA) disease. This study was conducted to investigate the association of plaque echostructure and other established and emerging cardiovascular risk factors with symptomatic ICA disease. Design: Cross-sectional study of consecutive patients with significant (> 50 %) ICA stenosis. Patients and methods: Carotid plaque echostructure, smoking, hypertension, diabetes mellitus, serum lipoprotein (a), homocysteine, vitamin B12, folate, cholesterol to high-density lipoprotein ratio, triglycerides, C-reactive protein, and the Framingham risk score were assessed in 124 consecutive patients (70 asymptomatic; 54 symptomatic) with significant (> 50 %) ICA stenosis. Results: The asymptomatic and symptomatic groups did not differ in terms of gender distribution (p = 0.76) and severity of stenosis (p = 0.62). Echolucent plaques (type 1 and 2) were more predominant in patients with symptomatic disease (p = 0.004, OR = 2.13, 95 % CI = 1.26-3.6). Patients with plaques type 1 were relatively younger than those with type 4 (p = 0.02). None of the other factors assessed had any significant association with symptomatic disease and any type of carotid plaque. Conclusions: Besides the severity of carotid stenosis, the presence of an echolucent plaque appears as an important factor associated with symptomatic ICA disease. Also, young patients are more likely to have an echolucent plaque suggesting an age-related association with plaque maturation.

Objective To establish whether treatment for three years with pro-juven progesterone cream affects progression of atherosclerotic plaques or bone density in postmenopausal women. Design Randomized double-blind placebo-controlled trial. Sample One hundred and thirty-one healthy postmenopausal women aged between 50 and 75 years with at least one asymptomatic arterial plaque visible on ultrasound of the carotid or femoral bifurcation. Methods Women were randomly allocated to receive pro-juven progesterone cream, 20 mg twice daily, or placebo, for three years. Main outcome measure Rate of change of plaque thickness, intima-media thickness and bone density of lumbar spine and femoral neck. Results There was no difference between the groups. Conclusion Pro-juven progesterone cream 20 mg twice daily did not affect progression of asymptomatic atherosclerosis or deterioration in bone density over three years.

Abstract The Cyprus Study is a prospective cohort study of cardiovascular disease (CVD). Its aim is to determine the relationship of intima–media thickness (IMT) of the common carotid (IMTcc), maximum thickness of IMT in the carotid bifurcation (IMTmax), number of carotid and femoral bifurcations with plaque and total plaque thickness (TPT) (sum of the maximum plaque measurements taken from the four bifurcations scanned) with the prevalence of clinical CVD. A total of 767 individuals (46% male) over the age of 40 years were recruited from a mountain village and a town outside the capital Nicosia. In addition to clinical examination, carotid and common femoral bifurcations were scanned with ultrasound. After controlling for conventional risk factors, there was little evidence of an association of IMTcc with CVD prevalence. However, IMTmax and TPT were associated with 2.9-fold (1.22 to 7.07) and 6.87-fold (2.42 to 19.43) increased odds of CVD prevalence, respectively. In conclusion, the TPT and number of bifurcations with plaque are more strongly associated with the prevalence of CVD. These findings warrant investigation in prospective studies to document associations with incident CVD events.

Context: Circulating IGF-I is inversely associated with ischemic heart disease incidence. Whether this association relates to alterations in plaque growth or stability, and the role of IGF-II and the major binding proteins [IGF binding protein (IGFBP)-2 and -3], is unclear. Objective: Our objective was to test the hypothesis that circulating IGF-I is inversely, and IGF-II is positively, associated with subclinical atherosclerosis and plaque stability. Design, Setting, and Participants: This was a cross-sectional analysis based on 310 participants in the United Kingdom-based Boyd Orr cohort who were aged 63–82 yr. Cohort members from Aberdeen, Bristol, Dundee, Wisbech, and London were invited to clinics for fasted venepuncture and arterial ultrasound examination. Main Outcomes: Arterial intima-media thickness, arterial plaque prevalence, and computerized assessment of plaque echogenicity (a measure of stability), undertaken using the gray scale median, were calculated. Results: In total, 269 of 310 (86.8%) participants had at least one carotid or femoral plaque. In models controlling for IGFBP-3, there was a 44% (95% confidence interval 12–64%) reduction in the odds of any plaque and a 28% lower (0–48%) odds of echolucent (unstable) plaques per sd increase in IGF-I. IGFBP-3 was positively associated with plaque instability (odds ratio: 1.38; 0.99–1.93). IGF-II was positively associated (0.05-mm increase per sd; 95% confidence interval 0.01–0.09), and IGFBP-2 was inversely associated, with carotid bifurcation intima-media thickness. Neither IGF-II nor IGFBP-2 was associated with plaque prevalence or echogenicity. Conclusion: High-circulating IGF-I levels may promote arterial plaque stability. IGF-II and IGFBP-2 do not appear to play a role in plaque development or stability.

The aim of this study was to evaluate the development of edema, and superficial and deep vein thrombosis (DVT) prophylaxis with an oral profibrinolytic agent (Flite Tabs, 150 mg pinokinase, Aidan, Tempe, AZ, USA) in long-haul flights (7-8 hours), in high-risk subjects. A group of 300 subjects was included; 76 were excluded for several problems including concomitant treat ments ; 204 were randomized into 2 groups (active treatment or placebo) to evaluate the effects of prophylaxis with Flite Tabs. An exercise program was used in both groups. The femoral, popliteal, tibial, and superficial veins were scanned with ultrasound before and within 90 minutes after flights. Of the included subjects, 92 of 103 controls and 94 of 101 treated subjects completed the study. Dropouts were due to connection problems. Age, gender, and risk distribution were comparable in the groups. In the treatment group, no DVT was observed. In the control group, 5 subjects (5.4%) had a DVT and there were 2 superficial thromboses (7 events in 92 subjects; 7.6%). At inclusion, edema was comparable in the 2 groups. After flights there was an increase in score in controls (+12%) in comparison with a decrease (-15%) in the Flite Tabs group (the difference in variation was statistically significant). Intention-to-treat analysis for thrombotic events shows 18 failures in controls (11 lost to follow-up + 7 throm botic events) of 92 subjects (19.6%) in comparison with 7 failures (of 94 subjects, equivalent to 7.4%) in the treatment group (p

In 20 patients with chronic venous insufficiency and venous hypertension associated with ulcerations, the effects of a new compound, applied onto the skin (Crystacide) were assessed in a randomized, controlled study. Duplex scanning was used to assess the presence of venous obstruction and incompetence, and microcirculatory methods were used to assess and quantify venous microangiopathy and to follow up subjects after local treatment with Crystacide. Laser Doppler flowmetry (LDF) was used to assess skin perfusion in association with transcutaneous (tc) partial pressure of oxygen (PO2) measurements. Local plasma free radicals (PFR) were evaluated in the area surrounding the venous ulcer, with the D-Rom test. Crystacide was applied around and on the ulcer for 10 days. Crystacide was more effective than the control treatment: PO2 was increased, PFR and LDF were decreased (flux increase is associated with venous hypertension), and the ulcer area was significantly smaller at 10 days in the Crystacide group in comparison with the placebo group (p < 0.05). In conclusion, in venous ulcerations, local treatment with Crystacide (10 days) improves the microcirculation and decreases skin free radicals improving healing.

Conventional cardiovascular risk factors have been used to identify subgroups at increased risk of cardiovascular events. The British Regional Heart Study Score (BRHSS) using such risk factors at best identifies only 59% of individuals that develop coronary heart disease (CHD) in the subsequent 5 years. To identify a high risk subgroup in the BRHS a new approach has been the use of ultrasound to study arterial wall thickening, presence or absence of plaques and plaque type, to try and increase the predictive value of the BRHS Score. Methods: Two towns (Dewsbury and Maidstone) of the British Regional Heart Study were selected because they have the highest and lowest prevalence of cardiovascular disease in the U.K respectively. A total of 418 men and 397 women were surveyed and their carotid and common femoral bifurcations scanned. Results: Total plaque thickness, carotid intima-media thickness (IMT), ultrasonic arterial score (UAS) and sum of plaque types reversed, were found to be the most significant explanatory variables in a multiple linear regression model with an r = 0.505 and R2 = 0.255. They could identify a subgroup of 25% of the population that contained 78% of cardiovascular deaths. Conclusion: These findings appear to suggest the presence of plaques, the collective information from the echomorphology of these lesions and their absolute measures are far more predictive of risk.

The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG), in comparison with placebo in 30 patients with superficial vein thrombosis (SVT). The 8-week study evaluated SVT with an analogue clinical/sympto matic score. SVT was associated with varicose veins. In patients treated with active EG the decrease in score was significantly larger (p < 0.02) than in the placebo group. No intolerance was observed. The decrease in score in the placebo group was due to spontaneous resolution and to skin manipulation and massage. In conclusion local treatment with EG in SVT improves signs/symptoms much faster than placebo. This study confirms earlier observation on the effective, local use of EG in SVT.

Microcirculatory changes in chronic venous insufficiency (CVI) due to venous hypertension produce venous hypertensive microangiopathy (VHM) and lead to ulceration. VHM is charac terized by enlarged, convoluted capillaries; increase in flux, permeability, and edema; and altered microlymphatics. PO2 is decreased and CO2 increased. Capillary exchanges are altered and nutritional alterations in association with microtrauma may cause venous ulcers. The aim of this pilot, cross-over, randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG) (single acute application) in 10 subjects with VHM and venous ulcers. The study was structured over 3 days: day 1 was used for the control evalua tion for all patients. One group was randomized for the sequence placebo (day 2) and EG the following day; the second group with the sequence EG (day 2) and placebo (day 3). Indepen dently from the sequence, measurements of flux and PO2 in standard conditions showed positive changes (significant decrease of the abnormally increased flux, PO2 increase) in the EG treatment group. Changes in the placebo group were limited and associated with skin manip ulation. In conclusion, EG acutely improves microcirculation in limbs with VHM and ulceration even with a single application.

The involvement of the microvascular structure in chronic venous insufficiency (CVI) causes venous hypertensive microangiopathy (VHM), which leads to venous ulceration. VHM is char acterized by enlarged and ramified capillaries, increased flux and capillary permeability, edema, and altered function of microlymphatics. TcPO2 is decreased and CO2 increased. This perfu sional paradox is caused by hyperperfusion in the deep skin layers with hypoperfusion of superficial nutritional capillaries. Exchanges in the capillary bed are altered. Nutritional skin alterations eventually lead to venous ulceration. Edema is the consequence of increased capillary pressure, reduced clearance, and by an increased exchange surface of capillaries. The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG) in 22 subjects with VHM due to severe varicose veins, treated with a single application. Measurements of flux, PO2 and PCO2 in standardized conditions of applica tion indicated a significant decrease of the abnormally increased flux and CO2; PO2 increased in the treatment group. Essaven gel, in comparison with placebo and controls acutely improves the microcirculation in VHM even with a single application.

The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG) in comparison with placebo in 30 patients with superficial vein thrombosis (SVT). The 4-week study evaluated the average skin temperature and an analogue symptomatic score. Below-knee SVT was associated with large varicose veins. In patients treated with active EG the decrease in score and in the average, composite skin temperature was significantly larger than in the placebo and control groups. No intolerance was observed. The decrease in score and temperature in the placebo group was mainly due to skin manipulation and massage. In conclusion, treatment with EG in SVT improves symptoms and decreases skin temperature faster. This study confirms earlier observations on the effective use of EG in SVT.

The involvement of the microcirculation in diabetic microangiopathy (DM) may be the cause of severe incapacitation and ulceration. DM is characterized by a diffuse increase in skin flux, reduction in venoarteriolar response, and increased permeability, resulting in edema. In this condition capillary exchanges are altered and nutritional alterations eventually lead to skin lesions and ulcers. The aim of this randomized, placebo-controlled study was to evaluate the effect of local (foot) treatment with Essaven gel (EG) in 15 subjects with DM and neuropathy and treated with local application of EG for 4 weeks. Measurements of composite, average laser Doppler (LDF) flux (ten measurements points), in standardized conditions showed a significant decrease in flux in the EG group. The flux decrease was present even after 1 week after the suspension of treatment. Changes in the control group were not significant. In the placebo group, variations were limited (associated with skin manipulation and gel application). In conclusion local treatment for 4 weeks with standardized application of EG improves the microcirculation in subjects with DM. The changes are detectable even 1 week after the end of the treatment period.

The involvement of the microcirculation in diabetic microangiopathy (DM) may be cause of severe invalidity and ulceration. Diabetic microangiopathy (DM) is characterized by a diffuse increase in skin flux, reduction in venoarteriolar response, and increased capillary permeability resulting in edema; skin PO2 is decreased and CO2 increased. In this condition, capillary exchanges are altered and nutritional alterations eventually lead to skin lesions and ulcers. The aim of this randomized, placebo-controlled study was to evaluate the effect of local foot care and treatment with Essaven gel (EG) in 30 subjects with DM and neuropathy and localized, small (

The involvement of the microcirculation in diabetic microangiopathy (DM) causes of severe incapacitation and ulceration. DM is characterized by a diffuse increase in flux, reduction in venoarteriolar response, associated with increased permeability resulting in edema and altered function of microlymphatics. In DM, skin PO2 is decreased and CO2 increased. In this condition capillary exchanges are altered and nutritional alterations eventually lead to skin lesions and ulcers. The aim of this randomized, placebo-controlled study was to evaluate the effect of local (foot) treatment with Essaven gel (EG) in 35 subjects with DM and neuropathy and localized, small (

The involvement of the microcirculation in chronic venous insufficiency (CVI) due to venous hypertension causes venous hypertensive microangiopathy (VHM) and venous ulceration. VHM is characterized by the presence of enlarged convoluted capillaries; microvascular thrombosis with obliteration of some capillaries; increase in flux, permeability, and edema; and altered function of microlymphatics. PO2 is decreased and CO2 increased. Capillary exchanges are altered, and nutritional alterations eventually lead to venous ulcers. Edema is associated with increased capillary pressure, reduced clearance, and an increased exchange surface of capillaries, which become tortuous and glomerular-like. The aim of this randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG) in 28 subjects with venous microangiopathy due to severe CVI and ulcers treated with a single acute application. Measurements of laser Doppler flux, PO2 and PCO2 in standardized conditions of application showed positive microcirculatory changes (significant decrease of the abnormally increased flux and CO2 while PO 2 increased) in the EG treatment group. Changes in the placebo and control group were more limited (changes in the placebo group were mainly associated with skin manipulation when placebo-EG was applied). ln conclusion, Essaven gel, in comparison with placebo, acutely improves the microcirculation in VHM even with a single application.

The aim of this study was to demonstrate whether total triterpenic fraction of Centella asiatica (TTFCA), was effective in improving the microcirculation in venous hypertension and microangiopathy. Forty patients with severe venous hypertension, ankle swelling, lipodermatosclerosis were included, After informed consent, patients were randomized into a treatment and a placebo group: those in the treatment group received TTFCA (tablets, 60 mg, twice daily for 8 weeks). The two groups of subjects were comparable for age and sex distribution. The mean age was 48 years (SD 9; M:F = 11:11) in the treatment group (22 patients) and 47.6 (SD 7; M:F = 10:8) in the placebo group (18 patients). There were no differences between placebo and treatment group at inclusion; there was no change between inclusion and measurements at 8 weeks in the placebo group. A decrease (p

A single-blind, placebo-controlled, randomized study was performed on the effects of different doses of the total triterpenic fraction of Centella asiatica (TTFCA) in patients with venous hypertensive microangiopathy. A combined microcirculatory model that considers laser Doppler flowmetry (LDF) and transcutaneous oxygen (PO2), transcutaneous carbon dioxide tension (PCO2) measurements was combined with the symptom evaluation. LDF tests included the baseline resting flow, the venoarteriolar reflex, and the variation of flow related to the temperature increase. All tests provided a significant difference between drug-treated groups and the placebo group, thereby allowing a distinction to be made between the higher (120 mg daily) and the lower (60 mg daily) dose of TTFCA. Transcutaneous PO2-PCO2 measurements were significantly modified by drug treatments, while no variation could be detected in the placebo group. Important Symptomatologic effects (evaluated by subjective scores) followed TTFCA administration, especially at the higher dose level, while no effect was obtained with placebo. The trend of symptom evaluation paralleled the results of objective tests of our microcirculatory model, providing evidence that this model can reveal effects of venoactive drugs on venous hypertensive microangiopathy. TTFCA displays a significant activity. Doses as high as 120 mg daily may be safely used in venous hypertension.

The aim of this prospective, randomized study was to demonstrate whether an oral preparation of TTFCA was effective in improving the microcirculation and edema (leg volume) in venous microangiopathy. Forty patients with venous hypertension were included. Treatment was prescribed for 6 weeks (tablets, 60 mg twice daily). Patients were randomized into a treatment and a placebo group. There were 20 patients in each group. In the treatment group the mean age was 42 (SD 7; M:F = 10:10); in the placebo group, the mean age was 40 (SD 9; M:F = 10:10). Tolerability and compliance were very good; there were no dropouts. At inclusion there were no differences between placebo and treatment group. After treatment there was a decrease in resting flux (29%) and an improvement (increase) in venoarteriolar response (52%); PO2 was increased (7.2%) and PCO2 decreased (9.6%). There was an important decrease in leg volume (66 mL decrease; 1.3% volume variation). The difference in flux, O2-CO2 and volume parameters were significant and clinically important at 6 weeks in the treatment group. In conclusion, TTFCA improves microcirculation and leg volume in venous hypertension. The effects of TTFCA are observed even in a limited sample of patients.

The aim of this study was to evaluate local capillary filtration with the vacuum suction chamber (VSC) and the rate of ankle swelling (RAS) in patients with ankle edema due to venous hypertension before and after treatment with oral TTFCA (60 mg tablets twice daily) for 4 weeks. Strain-gauge plethysmography (SGP) was used to assess RAS and local capillary filtration was studied with the VSC (applied on the perimalleolar region); the disappearance of the weal was measured (minutes). Fifty patients with chronic venous insufficiency and edema were included (M:F = 25:25) after informed consent and randomized into a treatment (mean age 43; SD 7) and a control (mean age 44; SD 8) group. Compliance was very good (100% completed the 4-week trial); no side effects were observed. The two groups were comparable for age/sex distribution. Values of RAS and VSC time were comparable in the two groups, at inclusion. After 4 weeks there were no changes in the control group. A significant reduction was observed in the treatment (RAS decreased to 34% of the initial value; the VSC time decreased 48%; p

The variation of capillary filtration rate (CFR), ankle circumference (AC), and ankle edema (AE) was evaluated in three groups of patients with venous hypertension (ambulatory venous pressure >42 mm Hg) and in a group of normal subjects before and after treatment for 4 weeks with total triterpenic fraction of Centella asiatica (TTFCA), a venoactive drug acting on the microcirculation and on capillary permeability. Group A (20 patients)was treated with TTFCA 60 mg thrice daily, group B (20 patients) was treated with 30 mg thrice daily; group C (12 patients) was treated with placebo; and group D (10 normal subjects) was treated with TTFCA 60 mg thrice daily in a randomized study. Capillary filtration rate was assessed by venous occlusion plethysmography, ankle edema by a new system called AET (ankle edema tester). Subjective symptoms of venous hypertension were assessed by an analogue scale line considering four symptoms: swelling sensation, restless lower extremity, pain and cramps, and tiredness. CFR, AC, and AE were significantly higher in patients in comparison with normal subjects. After 4 weeks of TTFCA treatment, there was a significant decrease of CFR, AC, and AET time in patients. This was also greater in the higher dose group. No significant change was observed in the placebo group and in normal subjects treated with TTFCA. Symptoms were also significantly improved in the two groups treated with the active drug according to the dose. No significant changes were observed in the placebo group. In conclusion, the improvement of signs and symptoms by TTFCA observed in patients with venous hypertension was well correlated with the improvement of CFR and ankle edema. Dose ranging showed that 180 mg/day is more effective in improving symptoms and CFR.

Noninvasive tests have been developed to provide qualitative and quantitative information that can offer answers to most questions posed in venous diseases. While duplex scanning is used to assess the macrocirculation, microcirculatory methods assess and quantify venous microangiopathy. Laser Doppler flowmetry is used to assess tissue viability and perfusion. Transcutaneous PO2 and PCO2 measurements are used to study venous hypertension, and strain-gauge plethysmography (SGP) is used to assess capillary filtration. In venous hypertension fluid filtration into the extracapillary compartment is increased. The increase in filtration is associated with a decreased venoarteriolar response. To quantify capillary filtration two methods have been developed: venous occlusion plethysmography and rate of ankle swelling. These methods quantify filtration into the extracapillary compartment and therefore are an indication of the formation of edema, which is the most frequent sign of venous hypertension. Other methods such as the vacuum suction chamber and the edema tester can be used to assess changes due to treatment in chronic venous hypertension. These methods have been used and validated in several experimental and clinical studies. The techniques described in this article were used in controlled environmental conditions. Results were consistent with clinical problems and data from previous studies from our group and from data from other investigators.

Background: Subclinical arteriosclerotic lesions at the carotid and femoral bifurcations may be related to the occurrence of future cardiovascular events and of occult arteriosclerotic coronary disease. B-mode ultrasound of carotid and femoral arteriosclerotic bifurcation lesions may provide a simple screening method to select asymptomatic subjects at risk of future events. Methods and results: 13 221 low-risk, healthy, asymptomatic individuals were included in a 10-year, prospective, follow-up based on carotid and femoral bifurcation morphology defined by B-mode ultrasound. Four classes were considered at inclusion (I: normal wall, II: wall thickening, III: non-stenosing plaques, IV: stenosing plaques). When 10 000 subjects (75.6% of included subjects; 6055 males, 3945 females) completed the 10-year follow-up the study was concluded. At 10 years there were 10 events (out of 7989 subjects) in class I and 81 events in II (930 subjects; incidence=8.6%); 239 events were observed in class III (611 subjects; 39.28%) and 381 events (470 subjects; 81.06%) in IV; 61 deaths occurred in classes III+IV (1081 subjects) producing a death rate within these two classes of 5.5% (51 out of 61=81.5% in class IV). The increased event rates in classes III and IV were significant (log rank; P

Erectile dysfunction (ED) can be associated with atherosclerotic disease. It is therefore important to be able to evaluate the extent of arterial disease. This includes subclinical arterial disease. We have developed a score based on high-resolution-B-mode ultrasound scanning of the carotid-femoral bifurcations. This is a cost-effective screening procedure that correlates well with the risk of cardiovascular events. The penile circulation can also be investigated to assess local circulation and the level of fibrosis. During this investigation it is worthwhile evaluating the carotid-femoral arteries because the risk factors that predict ED are the same as those for atherosclerosis. Penile fibrosis contributes to the pathogenesis of ED. Whether this change is associated with hypertension needs to be established by further studies.

Objective: The current commercially available sequential intermittent pneumatic compression device used for the prevention of deep venous thrombosis has a constant cycle of 11 seconds’ compression and 60 seconds’ deflation. This deflation period ensures that the veins are filled before the subsequent cycle begins. It has been suggested that in some positions (eg, semirecumbent or sitting) and with different patients (eg, those with venous reflux), refilling of the veins may occur much earlier than 60 seconds, and thus a more frequent cycle may be more effective in expelling blood proximally. The aim of the study was to test the effectiveness of a new sequential compression system (the SCD Response Compression System), which has the ability to detect the change in the venous volume and to respond by initiating the subsequent cycle when the veins are substantially full. Methods: In an open controlled trial at an academic vascular laboratory, the SCD Response Compression System was tested against the existing SCD Sequel Compression System in 12 healthy volunteers who were in supine, semirecumbent, and sitting positions. The refilling time sensed by the device was compared with that determined from recordings of femoral vein flow velocity by the use of duplex ultrasound scan. The total volume of blood expelled per hour during compression was compared with that produced by the existing SCD system in the same volunteers and positions. Results: The refilling time determined automatically by the SCD Response Compression System varied from 24 to 60 seconds in the subjects tested, demonstrating individual patient variation. The refilling time (mean ± SD) in the sitting position was 40.6 ± 10.0 seconds, which was significantly longer (P

The aim of this international multicenter trial was to evaluate the effects of a new surgical device (Gore External Valve Support-EVS) and technique for external valvuloplasty of the long saphenous vein (LSV). Patients with superficial venous disease and venous hyper tension due to pure superficial venous incompetence were randomized into two treatment groups, the first treated with "conventional treatment" (ligation or stripping) and the second with external valvuloplasty with the EVS. Patients with uncomplicated varicose veins within the age range of 35-65 years were included. Incompetence with presence of functional cusps at the saphenofemoral junction (SFJ), with vein dilatation were the main inclusion criteria. The EVS comprised of a GORE-TEX® patch material (including a nitinol frame) that is placed around the vein, producing a reduction in the caliber of the vein. Also the vein section becomes elliptical. These combined actions are aimed to reduce incompetence, allowing a better closure of the cusps. The EVS was placed at the SFJ after limited dissection of the vein and ligation of collaterals. The procedure was randomized as an alternative to simple ligation or stripping (according with the procedure commonly used in the center). The associated ligation of distal incom petent veins was allowed. The main outcome measures of the study were evaluated by color-duplex (morphologic findings and evaluation of reflux) and with ambulatory venous pressure (AVP) or air-plethysmography (APG). Main endpoints of the first year of the study and main subject of this report (mainly concerning safety within the first year of follow-up) were considered presence/absence of reflux; patency of the veins; mobility/function of vein cusps; occurrence of thrombosis; tolerability of the device; and increased complexity and operating time needed for the EVS. At 1 year 30 patients had been randomized (14 EVS implanted, 16 controls). Reflux was absent in all EVS patients, all treated veins were patent, and all cusps were mobile. No thrombosis had been observed and the tolerability of the device was very good. The increased complexity required by placing the EVS was limited (5-12 minutes more). In conclusion results of the first year show efficacy and tolerability of the EVS. In selected patients (superficial LSV incompetence, reflux-dilatation, functional SFJ cusps, incompetence mainly due to enlargement of the vein), the EVS could be an effective alternative to "destructive" ligation and/or stripping of the vein. Prolonged follow-up will indicate the clinical poten tials of the EVS.

Background and Purpose —B-mode ultrasound is a noninvasive method of examining the walls of peripheral arteries and provides measures of the intima-media thickness (IMT) at various sites (common carotid artery, bifurcation, internal carotid artery) and of plaques that may indicate early presymptomatic disease. The reported associations between cardiovascular risk factors, clinical disease, IMT, and plaques are inconsistent. We sought to clarify these relationships in a large, representative sample of men and women living in 2 British towns. Methods —The study was performed during 1996 in 2 towns (Dewsbury and Maidstone) of the British Regional Heart Study that have an ≈2-fold difference in coronary heart disease risk. The male participants were drawn from the British Regional Heart Study and were recruited in 1978–1980 and form part of a national cohort study of 7735 men. A random sample of women of similar age to the men (55 to 77 years) was also selected from the age-sex register of the general practices used in the original survey. A wide range of data on social, lifestyle, and physiological factors, cardiovascular disease symptoms, and diagnoses was collected. Measures of right and left common carotid IMT (IMT cca ) and bifurcation IMT (IMT bif ) were made, and the arteries were examined for plaques 1.5 cm above and below the flow divider. Results —Totals of 425 men and 375 women were surveyed (mean age, 66 years; range, 56 to 77 years). The mean (SD) IMT cca observed were 0.84 (0.21) and 0.75 (0.16) mm for men and women, respectively. The mean (SD) IMT bif were 1.69 (0.61) and 1.50 (0.77) mm for men and women, respectively. The correlation between IMT cca and IMT bif was similar in men ( r =0.36) and women ( r =0.38). There were no differences in mean IMT cca or IMT bif between the 2 towns. Carotid plaques were very common, affecting 57% (n=239) of men and 58% (n=211) of women. Severe carotid plaques with flow disturbance were rare, affecting 9 men (2%) and 6 women (1.6%). Plaques increased in prevalence with age, affecting 49% men and 39% of women aged 70 years. Plaques were most common among men in Dewsbury (79% affected) and least common among men in Maidstone (34% affected). IMT cca showed a different pattern of association with cardiovascular risk factors from IMT bif and was associated with age, SBP, and FEV 1 but not with social, lifestyle, or other physiological risk factors. IMT bif and carotid plaques were associated with smoking, manual social class, and plasma fibrinogen. IMT bif and carotid plaques were associated with symptoms and diagnoses of cardiovascular diseases. IMT bif associations with cardiovascular risk factors and prevalent cardiovascular disease appeared to be explained by the presence of plaques in regression models and in analyses stratified by plaque status. Conclusions —IMT cca , IMT bif , and plaque are correlated with each other but show differing patterns of association with risk factors and prevalent disease. IMT cca is strongly associated with risk factors for stroke and with prevalent stroke, whereas IMT bif and plaque are more directly associated with ischemic heart disease risk factors and prevalent ischemic heart disease. Our analyses suggest that presence of plaque, rather than the thickness of IMT bif , appears to be the major criterion of high risk of disease, but confirmation of these findings in other populations and in prospective studies is required. The association of fibrinogen with plaque appears to be similar to its association with incident cardiovascular disease. Further work elucidating the composition of plaques using ultrasound imaging would be helpful, and more data, analyzed to distinguish plaque from IMT bif and IMT cca , are required to understand the significance of thicker IMT in the absence of plaque.

Purpose: The value of ultrasonic plaque characteristics in identifying patients at “high-risk” of restenosis after percutaneous transluminal angioplasty (PTA) was studied. Methods: Thirty-one arterial stenoses (6 common iliac, 2 external iliac, 1 profunda femoris, 21 superficial femoral, and 1 popliteal) in 17 patients who underwent angioplasty were studied by means of duplex scanning. With a computer-based program, B-mode images were digitized and normalized using 2 reference points, blood and adventitia. A grey level of 0 to 5 was allocated for the lumen (blood) and 180 to 190 for the adventitia on a linear gray scale of 0 to 255 (0 = absolutely black; 255 = absolutely white), and the overall plaque gray-scale median (GSM) of the pixels of the plaque was used as a measure of plaque echodensity. After PTA, follow-up of stenoses was done on day 1, weekly for 8 weeks, at 3 months, 6 months, and 1 year. The total plaque thickness (sum of anterior and posterior components), minimal luminal diameter (MLD), and peak systolic velocity ratio (PSVR) were measured for all stenoses. An increase of more than 2 in the PSVR was the duplex criterion used to signify restenosis. Results: The GSM of the stenoses before angioplasty ranged from 6 to 71 (mean, 31.3 ± 17.9); 17 stenoses had a GSM less than 25 (mean, 18.7 ± 5.3), and 14 had a GSM more than 25 (mean, 46.4 ± 15.8). When the GSM was less than 25, the absolute reduction in plaque thickness on day 1 post-PTA was 3.3 ± 1.8 mm, in contrast to 1.8 ± 1.6 mm when GSM was more than 25 (P < .03). The restenosis rate (PSVR more than 2) was 41% at 6 months and remained unchanged at 1 year. When the GSM was less than 25, restenosis occurred in 11% of lesions, in comparison with 78% when the GSM was more than 25 (P < .001). Conclusion: Plaque echodensity can be used to evaluate stenoses before PTA, to predict initial success and identify a subgroup that has a high prevalence of restenosis. The identification of a group at “high-risk” of restenosis can improve the selection of patients for the procedure and also be used in prospective studies on the prevention of restenosis. (J Vasc Surg 1999;29:110-21.)

Three human aortic specimens were used for this in-vitro study on the effects of shock waves on the arterial wall. Specimen one was from a normal (for age) healthy aorta. The full abdominal lengh was used (including mesenteric and renal arteries and the aortoiliac bifurcation), divided into six pieces (3 cm). The pieces were placed and fixed into degassed water. Shock waves (SW) were focused onto the aortic wall by means of a B-mode ultrasound imager. An SW generator (Minilith SL1, Storz Medical AG, Kreuzlingen, Switzerland) was used for setting of energy flux density between 0.03 and 0.5 mJ/mm2. The six aortic pieces (excluding piece 1, placed in water and left untreated as control) were treated with SW at increasing energy levels. A second aortic specimen of a man with arteriosclerotic plaques was also used and the experiment repeated at energy levels 1, 5, and 8. Another specimen of normal thoracic aorta was exposed at energy levels 1 and 8 only. Energy levels delivered onto the aortic walls were selected from theoretically destructive levels to minimal levels known not to alter vascular tissues. High-resolution ultrasounds of the aortic segments were performed with a 10 MHz high- resolution, broad-band (ATL 3000, USA) probe in water before and after SW applica tion to detect structural changes in the wall after SW. Histology was performed with a standard hematoxylin-eosin staining. (Abstract continued) Results: The aortic pieces did not show macroscopic damages at visual examination, and at the ultrasound examination no visible changes were observed even at higher levels of SW energy. Also no effects were seen by histology. In conclusion, no damaging effects were observed, visually, by ultrasound, or by histology. At these energy levels SW appear to be safe and do not produce any damage to the aortic wall. Therefore, SW could be considered a safe, nondamaging procedure for potential treatment (ie, thrombolysis) in which vessel walls could be involved. Theoretically it is possible that functional changes could be observed in vivo including cell permeability modifications and other alterations (including changes in the potential of the cells in SW fields to modify themselves and to divide). At the energy levels described in this study SW could, theoretically be, safely used for vascular applications (ie, treating venous and arterial thrombi or in arterial plaques modification) without altering major, structural, arterial wall characteristics. Lesions or alterations that have a different density from the normal wall (thrombi or plaques) could be differently sensitive to the same dosage of SW. These differences in acoustic impedance characteristics could be used for potential treatments with SW without damaging the arterial wall.

Background: Determine the feasibility of studying the natural history of the atherosclerotic plaque following percutaneous transluminal angioplasty (PTA), using duplex scanning. Methods: Twenty-three patients with 40 stenoses (>70% and 2.0 was used to indicate >50% lumen diameter reduction. Results: Thirty stenoses were available for measurement and analysis. Mean reduction in plaque thickness after angioplasty was greater in echolucent plaques (2.33 ± 0.9 mm) than echogenic plaques (0.83 ± 0.6 mm; P 2.0) at 6 months was 12 of 30 (40%) remaining unchanged at 1 year; of the lesions that restenosed, 33% recurred before week 8 and the remainder between weeks 8 and 24, suggesting different mechanisms. During follow-up, all plaques showed “growth”; 2 mm in the remaining 13 (43%; group B). The incidence of restenosis (PSVR >2.0) was 4 of 17 (23%) in group A and 8 of 13 (61%) in group B ( P Conclusion: Duplex scanning provides valuable information on both luminal diameter and plaque thickness; it may be used to study the natural history of plaques following angioplasty and also the effects of therapeutic agents aimed at reducing restenosis.

Background: We aimed to explore the association between presence and number of components of the Metabolic Syndrome (MetS) and subclinical atherosclerosis outcomes (common carotid intima media thickness, plaque presence and sum of plaque area) in both the carotid and femoral bifurcations. Methods. Cross-sectional analysis of 771 volunteers from the ongoing epidemiological Cyprus Study (46% male; mean age = 60.1 ± 9.8). (a) Carotid intima-media thickness (IMTcc), (b) sum of plaque area in the carotid bifurcations (sum of the largest plaques in each carotid bifurcation-SPAcar), (c) sum of plaque area in the femoral bifurcations (sum of the largest plaques in each femoral bifurcation-SPAfem) and (d) sum of plaque area in both carotid and femoral bifurcations (sum of the areas of the largest plaques present in each of the four bifurcations-SPA) were measured at baseline using ultrasound. Presence and number of components of the MetS was ascertained using the National Cholesterol Education Program ATPIII definition and their association tested using multivariable regression models. Results: MetS was present in 259 (33.6%) individuals and was associated with a 0.02 mm increase in IMTcc (95% CI: 0.00 to 0.04, p = 0.047) after adjustment for age, sex, family history of CVD, alcohol consumption (BU/week) and smoking (pack-years). Each additional component of the MetS was associated with a 16% higher SPA (95% CI: 6.8% to 25.2%, p§ssub§for trend§esub§ = 0.001), a 10% higher SPAcar (95% CI: 5% to 24%, p§ssub§for trend§esub§ = 0.003) and a 14% higher SPAfem in the adjusted model. Conclusions: We confirm an association between the MetS and IMTcc as well as report for the first time an association between the MetS and its components and femoral plaque area, in a general population over 40 years of age. Having any risk factors for the MetS increases the risk for subclinical atherosclerosis, with the risk increasing with each additional component. Using the dichotomous definition of the MetS may be overlooking the risk for subclinical atherosclerosis -and by inference future cardiovascular events- associated with having less than 3 risk factors.

The stroke risk reduction benefit of surgical intervention in carotid occlusive disease has been validated in multicenter trials for various angiographically defined lesion severity categories. The two divergent angiographic grading methods used for internal carotid artery stenosis in these trials have caused confusion in the clinical application of their recommendations. Moreover, while today's highly accurate carotid duplex scanning can obviate the need for preoperative angiography in many cases, the duplex criteria must be tailored to achieve sufficiently reliable results on which therapeutic decisions can be made. This review offers a clarification of the discrepancies between the angiographic grading techniques and how their measurements of percent stenosis correlate to the duplex criteria needed to support the treatment decision-making process for carotid obliterative disease.

In the 1970s and 1980s, angiography was the standard method used for grading internal carotid artery stenosis. With the introduction of ultrasound in the 1980s and early 1990s, angiography became the gold standard used for the development of duplex velocity criteria for different grades of stenosis.

The multidisciplinary approach combining angiography, high-resolution ultrasound imaging, transcranial Doppler studies of embolic signals, plaque pathology, histochemistry, coagulation studies, and, more recently, molecular biology has led to a better understanding of the mechanism of carotid plaque rupture, the key mechanism underlying the development of cerebrovascular events1–3 (Chap. 1).