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Carotid Plaques (carotid + plaque)
Selected AbstractsVisual Analysis or Semi-Automated Gray-Scale-Based Color Mapping of the Carotid Plaque: Which Method Correlates the Best with the Presence of Cerebrovascular Symptoms and/or Lesions on MRI?JOURNAL OF NEUROIMAGING, Issue 2 2009Isabelle Momjian MD ABSTRACT BACKGROUND AND PURPOSE To determine the correlation between carotid plaque morphology, assessed by two different ultrasonographic methods, and presence of cerebrovascular events and/or lesions on magnetic resonance imaging (MRI). PATIENTS AND METHODS Visual analysis of plaque echogenicity using a five-type classification was performed. Further, a semi-automated gray-scale-based color mapping of the whole plaque and of its surface was achieved. RESULTS There were 31 (35%) symptomatic (23 strokes and 8 transitory ischemic attacks [TIAs]) and 58 (65%) asymptomatic carotid stenoses. MRI lesions related to the carotid stenosis if located in the ipsilateral cortical, subcortical, or watershed area, were present in 27 cases (30%). In a multivariate logistic regression model, degree of stenosis (P= .03) and a predominant red color on the surface (P= .04) were independent factors associated with the presence of cerebrovascular events and/or lesions on MRI. Sensitivity and specificity were, respectively, 80% and 63% by combining degree of stenosis and color mapping of plaque surface. CONCLUSION Degree of stenosis and a predominant red color on plaque surface were independent factors associated with the presence of cerebrovascular events and/or lesions on MRI. No correlation was observed with any particular type of plaque based on visual analysis alone. [source] Point/Counterpoint: The Role of Carotid UltrasoundPREVENTIVE CARDIOLOGY, Issue 2 2005Point: Uses Of Carotid Plaque Measurement As A Predictor Of Cardiovascular Events Vascular prevention is most cost-effective in high-risk patients, but secondary prevention misses many opportunities. The high-risk strategy-identifying patients with high levels of risk factors-is problematic because traditional risk factors predict only half of vascular events. In multiple regression, traditional risk factors explained only half of carotid atherosclerosis. New strategies are being explored, such as electron-beam computerized tomographic measurement of coronary calcification, to identify high-risk patients. Carotid plaque is a powerful tool for identifying and managing high-risk vascular patients, as it explains twice as much of unexplained vascular risk as coronary calcium by electron beam computerized tomography, and it has significant advantages compared with intimal-medial thickness. After adjustment for risk factors, patients in the highest quartile of baseline plaque area have 3.5 times the risk of stroke, death, or myocardial infarction compared with those in the lowest quartile. Those with regression or stable plaque have half the risk of those with progression after adjustment for the same panel of risk factors. The therapeutic target is plaque regression or stabilization, not just control of traditional risk factors. Trying to treat arteries without measuring plaque is like trying to treat hypertension without measuring the pressure, or hyperlipidemia without measuring the lipids. [source] Carotid plaque computed tomography imaging in stroke and nonstroke patientsANNALS OF NEUROLOGY, Issue 2 2008Max Wintermark MD Objective To identify a set of computed tomographic (CT) features of carotid atherosclerotic plaques that is significantly associated with ischemic stroke. Methods In a cross-sectional study, we retrospectively identified 136 consecutive patients admitted to our emergency department with suspected stroke who underwent a CT-angiogram of the carotid arteries. CT-angiographic studies of the carotid arteries were processed automatically using automated computer classifier algorithm that quantitatively assesses a battery of carotid CT features. Acute stroke patients were categorized into "acute carotid stroke patients" and "nonacute carotid stroke patients" independent of carotid wall CT features, using the Causative Classification System for Ischemic Stroke, which includes the neuroradiologist's review of the imaging studies of the brain parenchyma and of the degree of carotid stenosis, and charted test results (such as electrocardiogram). Univariate followed by multivariate analyses were used to build models to differentiate between these patient groups and to differentiate between the infarct and unaffected sides in the "acute carotid stroke patients." Results Forty "acute carotid stroke" patients and 50 "nonacute carotid stroke" patients were identified. Multivariate modeling identified a small number of the carotid wall CT features that were significantly associated with acute carotid stroke, including wall volume, fibrous cap thickness, number and location of lipid clusters, and number of calcium clusters. Interpretation Patients with acute carotid stroke demonstrate significant differences in the appearance of their carotid wall ipsilateral to the side of their infarct, when compared with either nonacute carotid stroke patients or the carotid wall contralateral with the infarct side. Ann Neurol 2008;64:149,157 [source] Differences in the detection of cyclo-oxygenase 1 and 2 proteins in symptomatic and asymptomatic carotid plaquesBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2001S. M. Wijeyaratne Background: The expression of cyclo-oxygenase (COX) 1 and 2 has been demonstrated in atherosclerotic arteries. In the present study this was correlated with symptoms arising from a carotid plaque. Methods: Carotid plaques from 12 asymptomatic patients were compared with 11 plaques from patients who had had neurological symptoms within the preceding 30 days. Sections were stained with haematoxylin and eosin, elastin van Gieson and goat antihuman antibodies to COX-1 and COX-2. Plaque morphology was correlated with neurological symptoms. The area with positive COX-1 and COX-2 staining was measured by computerized planimetry in entire cross-sections and in specific areas of the plaque. Results: There was a significant association between cap thinning and plaque rupture with symptoms (P = 0·003). The percentage area of positive staining in entire cross-sections for both COX-1 and COX-2 was significantly greater in symptomatic plaques (P = 0·001 and 0·0004 respectively). Staining in symptomatic plaques was significantly greater in the cap (COX-1: P = 0·001; COX-2: P = 0·0001) and shoulder (COX-1: P = 0·008; COX-2: P = 0·007) regions of the plaque. COX-1 expression in the sclerotic area was not increased (P = 0·15) although COX-2 staining was significantly greater (P = 0·04). Conclusion: Both COX-1 and COX-2 detection was increased in symptomatic plaques. COX may contribute to plaque rupture and the onset of symptoms. © 2001 British Journal of Surgery Society Ltd [source] Comparison of lipid-rich necrotic core size in symptomatic and asymptomatic carotid atherosclerotic plaque: Initial resultsJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2008Vincent C. Cappendijk MD Abstract Purpose To investigate the potential difference in the size of the lipid-rich necrotic core (LRNC) in carotid plaques of symptomatic patients versus asymptomatic patients. Pathological studies established that a large LRNC is an important feature of vulnerable atherosclerotic plaque. Previously, we have demonstrated a high correlation between semiquantitative analysis of the LRNC size in T1-weighted (w) turbo field echo (TFE) MR images and histology. Materials and Methods Thirty-seven patients with carotid stenosis >70% with (n = 26) or without (n = 11) symptoms were included. Three independent MR readers quantified the amount of LRNC with a T1w TFE pulse sequence. The relative amount of LRNC (LRNC score) was defined as sum of cross-sectional area percentages LRNC per carotid plaque. Results Interreader agreement for the three MR readers was good, with an intraclass correlation coefficient (ICC, 95% confidence interval [CI]) of 0.72 (0.57,0.83). All three MR readers on average found a larger LRNC in the symptomatic group of patients, although this was not statistically significant. The mean LRNC score was 116 ± 129 and 59 ± 62 for symptomatic and asymptomatic patients, respectively (P = 0.13). Symptomatic patients showed wide ranges in LRNC scores (0,424), while the range was much lower in the asymptomatic group (0,170). Conclusion Single-sequence T1w TFE may be a promising technique to study atherosclerotic plaque at risk of stroke. Larger studies are warranted to confirm these promising results. J. Magn. Reson. Imaging 2008;27:1356,1361. © 2008 Wiley-Liss, Inc. [source] Dysfunctional proinflammatory high-density lipoproteins confer increased risk of atherosclerosis in women with systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 8 2009Maureen McMahon Objective Women with systemic lupus erythematosus (SLE) have an increased risk of atherosclerosis. Identification of at-risk patients and the etiology underlying atherosclerosis in SLE remain elusive. The antioxidant capacity of normal high-density lipoproteins (HDLs) is lost during inflammation, and these dysfunctional HDLs might predispose individuals to atherosclerosis. The aim of this study was to determine whether dysfunctional proinflammatory HDL (piHDL) is associated with subclinical atherosclerosis in SLE. Methods Carotid artery ultrasound was performed in 276 women with SLE to identify carotid plaques and measure intima-media thickness (IMT). The antioxidant function of HDL was measured as the change in oxidation of low-density lipoprotein after the addition of HDL cholesterol. Two antiinflammatory HDL components, paraoxonase 1 and apolipoprotein A-I, were also measured. Results Among the SLE patients, 48.2% were determined to have piHDL on carotid ultrasound, while 86.7% of patients with plaque had piHDL compared with 40.7% of those without plaque (P < 0.001). Patients with piHDL also had a higher IMT (P < 0.001). After multivariate analysis, the only factors found to be significantly associated with plaque were the presence of piHDL (odds ratio [OR] 16.1, P < 0.001), older age (OR 1.2, P < 0.001), hypertension (OR 3.0, P = 0.04), dyslipidemia (OR 3.4, P = 0.04), and mixed racial background (OR 8.3, P = 0.04). Factors associated with IMT measurements in the highest quartile were the presence of piHDL (OR 2.5, P = 0.02), older age (OR 1.1, P < 0.001), a higher body mass index (OR 1.07, P = 0.04), a cumulative lifetime prednisone dose ,20 gm (OR 2.9, P = 0.04), and African American race (OR 8.3, P = 0.001). Conclusion Dysfunctional piHDL greatly increases the risk of developing subclinical atherosclerosis in SLE. The presence of piHDL was associated with an increased prevalence of carotid plaque and with a higher IMT. Therefore, determination of piHDL may help identify patients at risk for atherosclerosis. [source] Rate and determinants of progression of atherosclerosis in systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 10 2007Mary J. Roman Objective To determine the rate of atherosclerosis progression as well as the relationship of traditional risk factors, systemic lupus erythematosus (SLE),related factors, and treatment to atherosis progression in SLE patients. Methods Outpatients in the Hospital for Special Surgery SLE Registry underwent serial carotid ultrasound and clinical assessment in a longitudinal study. Results Among 158 patients, 77 (49%) had persistent absence of atherosclerosis (carotid plaque), 36 (23%) had unchanged atherosclerosis, and 45 (28%) had progressive atherosclerosis, defined as a higher plaque score (new plaque in 25 patients and more extensive plaque in 20 patients) after a mean ± SD interval of 34 ± 9 months. Multivariate determinants of atherosclerosis progression were age at diagnosis (odds ratio [OR] 2.75, 95% confidence interval [95% CI] 1.67,4.54 per 10 years, P < 0.001), duration of SLE (OR 3.16, 95% CI 1.64,6.07 per 10 years, P < 0.001), and baseline homocysteine concentration (OR 1.24, 95% CI 1.06,1.44 per ,moles/liter, P = 0.006). SLE patients with stable plaque and progressive plaque differed only in baseline homocysteine concentration. Atherosclerosis progression was increased across tertiles of homocysteine concentration (16.2%, 36.4%, and 56.1%; P = 0.001), and homocysteine tertile was independently related to progression of atherosclerosis (OR 3.14, 95% CI 1.65,5.95 per tertile, P < 0.001). Less aggressive immunosuppressive therapy and lower average prednisone dose were associated with progression of atherosclerosis in univariate, but not multivariate, analyses. Inflammatory markers and lipids were not related to atherosclerosis progression. Conclusion Atherosclerosis develops or progresses in a substantial minority of SLE patients during short-term followup (10% per year on average). Older age at diagnosis, longer duration of SLE, and higher homocysteine concentration are independently related to progression of atherosclerosis. These findings show that aggressive control of SLE and lowering of homocysteine concentrations are potential means to retard the development and progression of atherosclerosis in SLE. [source] Differences in the detection of cyclo-oxygenase 1 and 2 proteins in symptomatic and asymptomatic carotid plaquesBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2001S. M. Wijeyaratne Background: The expression of cyclo-oxygenase (COX) 1 and 2 has been demonstrated in atherosclerotic arteries. In the present study this was correlated with symptoms arising from a carotid plaque. Methods: Carotid plaques from 12 asymptomatic patients were compared with 11 plaques from patients who had had neurological symptoms within the preceding 30 days. Sections were stained with haematoxylin and eosin, elastin van Gieson and goat antihuman antibodies to COX-1 and COX-2. Plaque morphology was correlated with neurological symptoms. The area with positive COX-1 and COX-2 staining was measured by computerized planimetry in entire cross-sections and in specific areas of the plaque. Results: There was a significant association between cap thinning and plaque rupture with symptoms (P = 0·003). The percentage area of positive staining in entire cross-sections for both COX-1 and COX-2 was significantly greater in symptomatic plaques (P = 0·001 and 0·0004 respectively). Staining in symptomatic plaques was significantly greater in the cap (COX-1: P = 0·001; COX-2: P = 0·0001) and shoulder (COX-1: P = 0·008; COX-2: P = 0·007) regions of the plaque. COX-1 expression in the sclerotic area was not increased (P = 0·15) although COX-2 staining was significantly greater (P = 0·04). Conclusion: Both COX-1 and COX-2 detection was increased in symptomatic plaques. COX may contribute to plaque rupture and the onset of symptoms. © 2001 British Journal of Surgery Society Ltd [source] Serum interleukin-6 is elevated in symptomatic carotid bifurcation diseaseACTA NEUROLOGICA SCANDINAVICA, Issue 2 2009M. Koutouzis Introduction,,, The levels of circulating proinflammatory cytokines may express the extent of the inflammatory response and their participation in plaque progression and rupture needs to be evaluated. We aimed to investigate differences in circulating levels of proinflammatory cytokines and in plaque infiltration by macrophages between patients undergoing carotid endarterectomy for symptomatic and asymptomatic carotid atherosclerotic disease. Methods,,, One hundred nineteen patients (91 men and 28 women; mean age 66 ± 8 years; range 42,83 years) who underwent carotid endarterectomy for significant (>70%) carotid bifurcation stenosis were enrolled in this study. Patients were characterized as symptomatic (n = 62) or asymptomatic (n = 57) after neurological examination. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-, (TNF-,), IL-1,, serum amyloid A (SAA), and high-sensitivity C-reactive protein (hs-CRP) were evaluated. Macrophage infiltration of the plaque was assessed quantitatively from endarterectomy specimens using the monoclonal antibody CD68. Results,,, Serum IL-6 levels were significantly higher in patients with symptomatic compared with those with asymptomatic carotid disease (3.3 [2.0,6.5] pg/ml vs 2.5 [1.9,4.1] pg/ml, P = 0.02). TNF-,, IL-1,, SAA, and hs-CRP levels did not differ significantly between the two groups. Symptomatic patients had also more intense macrophage accumulation in the carotid plaque compared with asymptomatic patients (0.6 ± 0.1% vs 0.4 ± 0.1%, P < 0.001). Although there were correlations between the levels of the different inflammatory markers, there were no correlation between any of them and the extent of plaque macrophage infiltration. Conclusion,,, Patients with symptomatic carotid atherosclerotic disease have elevated serum IL-6 levels compared with asymptomatic patients. Symptomatic patients have also more intense macrophage infiltration of the atherosclerotic plaque suggesting that inflammatory process may contribute to the destabilization of the carotid plaque. [source] Combined Effects of Glycated Hemoglobin A1c and Blood Pressure on Carotid Artery Atherosclerosis in Nondiabetic PatientsCLINICAL CARDIOLOGY, Issue 9 2010Wen Zhu MD Background The relationship between HbA1c, blood pressure, and carotid atherosclerosis in nondiabetic patients is not clear. Hypothesis HbA1c and blood pressure can affect carotid-artery atherosclerosis in nondiabetic patients. Methods This retrospective cross-sectional study included 216 patients without diabetes mellitus. A positive carotid ultrasonographic result was defined as intima-media thickness of the common carotid artery , 0.9 mm, or presence of carotid plaque. Results Compared with patients without carotid atherosclerosis, patients with carotid atherosclerosis had significantly higher levels of HbA1c and systolic blood pressure (SBP). Higher levels of HbA1c and SBP were found to be associated with increased carotid atherosclerosis. Given similar SBP levels, higher HbA1c (>5.6%) was also related to increased carotid atherosclerosis. In multiple logistic regression analysis, HbA1c (odds ratio: 4.1, P = 0.009) emerged as the only statistically significant modifiable factor that was associated with carotid atherosclerosis, independent of smoking, body mass index, fasting plasma glucose, 2-hour plasma glucose, SBP, diastolic blood pressure, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Conclusions Our study shows that a slight increase of HbA1c may associate with carotid atherosclerosis in nondiabetic patients. Moreover, the coexistence of an elevated SBP level and a slightly increased HbA1c level may have a more significant effect on carotid atherosclerosis. Copyright © 2010 Wiley Periodicals, Inc. Dr. Zhu and Dr. Sun contributed equally to this work. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Coats AJ. Ethical authorship and publishing. Int J Cardiol. 2009;131:149,150). This work was supported by a Chinese National Science Grant to Dr. Yong Li (Grant No. 30873350). The authors have no other funding, financial relationships, or conflicts of interest to disclose. [source] Thrombogenic and atherogenic activities of lysophosphatidic acidJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2004Wolfgang Siess Abstract Lysophosphatidic acid (LPA) has been identified as a biologically active lipid in mildly-oxidized LDL, human atherosclerotic lesions, and the supernatant of activated platelets. The evidence that LPA has thrombogenic and atherogenic activities has increased substantially in recent years. Supporting the thrombogenic activity of LPA, analysis of the core region of human carotid plaques revealed recently the presence of alkyl- and acyl-molecular species from LPA with high platelet-activating potency (16:0 alkyl-LPA, 20:4 acyl-LPA). LPA, lipid extracts of atherosclerotic plaques, and the lipid-rich core elicited shape change and, in synergy with other platelet stimuli, aggregation of isolated platelets. This effect was completely abrogated by prior incubation of platelets with LPA receptor antagonists. Furthermore, LPA at concentrations approaching those found in vivo, induced platelet shape change, aggregation, and platelet-monocyte aggregate formation in blood. LPA-stimulated platelet aggregation was mediated by the ADP-stimulated activation of the P2Y1 and P2Y12 receptors. Supporting its atherogenic activity, LPA is a mitogen and motogen to vascular smooth muscle cells (VSMCs) and an activator of endothelial cells and macrophages. Recently, LPA has been identified as an agonist of the peroxisome proliferator activating receptor , (PPAR,), which is a key regulator of atherogenesis. LPA elicits progressive neointima formation, which is fully abolished by GW9662, an antagonist of PPAR,. We propose that LPA plays a central role in eliciting vascular remodeling and atherogenesis. Furthermore, upon rupture of lipid-rich atherosclerotic plaques, LPA may trigger platelet aggregation and intra-arterial thrombus formation. Antagonists of LPA receptors might be useful in preventing LPA-elicited thrombus formation and neointima formation in patients with cardiovascular diseases. © 2004 Wiley-Liss, Inc. [source] Circulating matrix metalloproteinase 9 levels in relation to sampling methods, femoral and carotid atherosclerosisJOURNAL OF INTERNAL MEDICINE, Issue 6 2008F. J. Olson Abstract. Objectives., To examine whether circulating levels of matrix metalloproteinase 9 (MMP-9) were associated with ultrasound-assessed intima-media thickness (IMT) and echolucent plaques in the carotid and femoral arteries. To examine preanalytical sources of variability in MMP-9 concentrations related to sampling procedures. Subjects and design., Plasma and serum MMP-9 levels were compared with ultrasound assessed measures of femoral and carotid atherosclerosis, in a cross-sectional study of 61-year-old men (n = 473). Preanalytical sources of variability in MMP-9 levels were examined in 10 healthy subjects. Main outcome measures were circulating levels of MMP-9 in serum and plasma, IMT of the carotid and femoral arteries, and plaque status based on size and echolucency. Setting., Research unit at university hospital. Results., Plasma concentrations of total and active MMP-9 were associated with femoral artery IMT independently of traditional cardiovascular risk factors, and were higher in subjects with moderate to large femoral plaques. Plasma MMP-9 concentration was higher in men with echolucent femoral plaques (P = 0.006) compared with subjects without femoral plaques. No similar associations were found for carotid plaques. MMP-9 concentrations were higher in serum than in plasma, and higher when sampling was performed with Vacutainer than with syringe. MMP-9 levels in serum were more strongly associated with peripheral neutrophil count compared with MMP-9 levels in plasma. Conclusions., Plasma MMP-9 levels were associated with atherosclerosis in the femoral artery, and total MMP-9 concentration was higher in men with echolucent femoral plaques. The choice of sample material and sampling method affect the measurements of circulating MMP-9 levels. [source] Comparison of lipid-rich necrotic core size in symptomatic and asymptomatic carotid atherosclerotic plaque: Initial resultsJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2008Vincent C. Cappendijk MD Abstract Purpose To investigate the potential difference in the size of the lipid-rich necrotic core (LRNC) in carotid plaques of symptomatic patients versus asymptomatic patients. Pathological studies established that a large LRNC is an important feature of vulnerable atherosclerotic plaque. Previously, we have demonstrated a high correlation between semiquantitative analysis of the LRNC size in T1-weighted (w) turbo field echo (TFE) MR images and histology. Materials and Methods Thirty-seven patients with carotid stenosis >70% with (n = 26) or without (n = 11) symptoms were included. Three independent MR readers quantified the amount of LRNC with a T1w TFE pulse sequence. The relative amount of LRNC (LRNC score) was defined as sum of cross-sectional area percentages LRNC per carotid plaque. Results Interreader agreement for the three MR readers was good, with an intraclass correlation coefficient (ICC, 95% confidence interval [CI]) of 0.72 (0.57,0.83). All three MR readers on average found a larger LRNC in the symptomatic group of patients, although this was not statistically significant. The mean LRNC score was 116 ± 129 and 59 ± 62 for symptomatic and asymptomatic patients, respectively (P = 0.13). Symptomatic patients showed wide ranges in LRNC scores (0,424), while the range was much lower in the asymptomatic group (0,170). Conclusion Single-sequence T1w TFE may be a promising technique to study atherosclerotic plaque at risk of stroke. Larger studies are warranted to confirm these promising results. J. Magn. Reson. Imaging 2008;27:1356,1361. © 2008 Wiley-Liss, Inc. [source] Albumin-bound low molecular weight thiols analysis in plasma and carotid plaques by CEJOURNAL OF SEPARATION SCIENCE, JSS, Issue 1 2010Angelo Zinellu Abstract We describe a new method for the quantification of low molecular weight thiols, as homocysteine, cysteine, cysteinylglycine, glutamylcysteine and glutathione bound to human plasma albumin. After albumin isolation and purification by SDS-PAGE, thiols were freed from protein with tri- n -butylphosphine and successively derivatized with 5-iodoacetamidofluorescein. Samples were then injected and quantified in about 18,min by CE with laser induced fluorescence detection. Precision tests indicate a good repeatability of the method both for migration times (RSD<0.63%) and areas (RSD<2.98%). The method allows to measure all five low molecular weight thiols released from just 3,,g of albumin thus improving the other described methods in which only three or four thiols were detected. Due to the elevated sensitivity (LOD of 0.3,pM for all thiols), also low molecular weight thiols bound to albumin filtered in tissues could be quantified. [source] Independent association of matrix metalloproteinase-10, cardiovascular risk factors and subclinical atherosclerosisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2007J. ORBE Summary.,Objectives: Circulating levels of matrix metalloproteinase (MMP)-10 are related to inflammation in asymptomatic subjects with cardiovascular risk factors. Whether MMP-10 is associated with the severity of atherosclerosis remains to be determined. This study examines the relationship of systemic MMP-10 levels with atherosclerotic risk factors and subclinical atherosclerosis. Methods and results: Circulating levels of MMP-1, -9 and -10, and markers of inflammation [fibrinogen, interleukin-6, von Willebrand factor, and high-sensitivity C-reactive protein (hs-CRP)] were measured in 400 subjects (mean age 54.3 years, 77.7% men) with cardiovascular risk factors but free from clinical cardiovascular disease. Subclinical atherosclerosis was evaluated by both the mean carotid intima-media thickness (IMT) and the presence of atherosclerotic plaques with the use of B-mode ultrasound in all subjects. MMP-10 levels were positively correlated with fibrinogen (r = 0.24, P < 0.001), hs-CRP (r = 0.14, P < 0.01) and carotid IMT (r = 0.17, P < 0.01). The association between MMP-10 and IMT remained significant in multiple regression analysis (P < 0.02) when controlling for traditional atherosclerotic risk factors and inflammatory markers. Such an association was not observed for MMP-1 and -9. Subjects in the highest MMP-10 tertile had significantly higher carotid IMT (adjusted odds ratio 6.3, 95% confidence interval 1.3,31.4, P = 0.024). In addition, MMP-10 levels were significantly higher in patients with carotid plaques (n = 78) than in those with no plaques after adjusting for age and sex (P < 0.01). Conclusion: Higher serum MMP-10 levels were associated with inflammatory markers, increased carotid IMT and atherosclerotic plaques in asymptomatic subjects. Circulating MMP-10 may be useful to identify subclinical atherosclerosis in subjects free from cardiovascular disease. [source] Role of Chlamydia pneumoniae -infected macrophages in atherosclerosis developments of the carotid arteryNEUROPATHOLOGY, Issue 1 2003Satoshi Kuroda Chlamydia pneumoniae (C. pneumoniae) infection has been recently accepted as an important cause of atherosclerosis. However, the precise mechanisms remain unclear. The present study was aimed to clarify the distribution link among C. pneumoniae, chlamydial HSP 60, and activated macrophages. Atheromatous carotid plaques were obtained from 40 consecutive carotid endarterectomies (CEA). The specimens were prepared for HE and elastica,van Gieson staining. Parallel sections were stained immunocytochemically with monoclonal antibodies for a C. pneumoniae -specific antigen, chlamydial HSP 60, activated macrophages, and smooth muscle cells. Immunoreactivity for the C. pneumoniae -specific antigen was observed within the endothelial cells, activated macrophages, and smooth muscle cells in 36 of 40 specimens (90%). Chlamydial HSP 60 was found in all specimens positive for the C. pneumoniae -specific antigen, and mainly co-localized with the C. pneumoniae -specific antigen within the activated macrophages. The present results suggest that C. pneumoniae is a key microbial organ that causes atheroma developments in the carotid artery. Chlamydia pneumoniae -infected macrophages may come into the arterial intima and mediate inflammatory and autoimmune processes through the production of chlamydial HSP 60, leading to atherosclerosis. [source] Dysfunctional proinflammatory high-density lipoproteins confer increased risk of atherosclerosis in women with systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 8 2009Maureen McMahon Objective Women with systemic lupus erythematosus (SLE) have an increased risk of atherosclerosis. Identification of at-risk patients and the etiology underlying atherosclerosis in SLE remain elusive. The antioxidant capacity of normal high-density lipoproteins (HDLs) is lost during inflammation, and these dysfunctional HDLs might predispose individuals to atherosclerosis. The aim of this study was to determine whether dysfunctional proinflammatory HDL (piHDL) is associated with subclinical atherosclerosis in SLE. Methods Carotid artery ultrasound was performed in 276 women with SLE to identify carotid plaques and measure intima-media thickness (IMT). The antioxidant function of HDL was measured as the change in oxidation of low-density lipoprotein after the addition of HDL cholesterol. Two antiinflammatory HDL components, paraoxonase 1 and apolipoprotein A-I, were also measured. Results Among the SLE patients, 48.2% were determined to have piHDL on carotid ultrasound, while 86.7% of patients with plaque had piHDL compared with 40.7% of those without plaque (P < 0.001). Patients with piHDL also had a higher IMT (P < 0.001). After multivariate analysis, the only factors found to be significantly associated with plaque were the presence of piHDL (odds ratio [OR] 16.1, P < 0.001), older age (OR 1.2, P < 0.001), hypertension (OR 3.0, P = 0.04), dyslipidemia (OR 3.4, P = 0.04), and mixed racial background (OR 8.3, P = 0.04). Factors associated with IMT measurements in the highest quartile were the presence of piHDL (OR 2.5, P = 0.02), older age (OR 1.1, P < 0.001), a higher body mass index (OR 1.07, P = 0.04), a cumulative lifetime prednisone dose ,20 gm (OR 2.9, P = 0.04), and African American race (OR 8.3, P = 0.001). Conclusion Dysfunctional piHDL greatly increases the risk of developing subclinical atherosclerosis in SLE. The presence of piHDL was associated with an increased prevalence of carotid plaque and with a higher IMT. Therefore, determination of piHDL may help identify patients at risk for atherosclerosis. [source] Vascular endothelial growth factor is associated with histological instability of carotid plaques,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 5 2008D. A. Russell Background: Vascular endothelial growth factor (VEGF) promotes events favouring carotid plaque instability: inflammatory chemoattraction, thrombogenesis, and upregulation of matrix metalloproteinases and cell adhesion molecules. The aim of this study was to assess neovascularization, VEGF and its receptors in high-grade stable and unstable carotid plaques. Methods: Immunohistochemical staining for CD34, VEGF, VEGF receptor (VEGFR) 1 and VEGFR2 was performed in 34 intact carotid endarterectomy specimens, and compared in sections demonstrating maximal histological instability (cap rupture/thinning) or, if stable, maximal stenosis. Results: VEGF staining was increased in 12 unstable compared with 22 stable plaques (median (interquartile range, i.q.r.) plaque score 4·0 (4·0,4·0) versus 3·0 (2·0,3·0); P = 0·002) with upregulation of VEGFR1 (plaque score 4·0 (2·0,4·0) versus 2·0 (1·0,3·0); P = 0·016). In unstable plaques this was associated with increased microvessel density in the cap (median (i.q.r.) 12·1 (4·0,30·0) versus 1·1 (0·0,7·3) microvessels/mm2; P = 0·017) and shoulder regions (7·7 (3·4,21·4) versus 3·1 (0·4,10·8) microvessels/mm2; P = 0·176). Conclusion: Increased VEGF and receptor staining were seen in histologically unstable carotid plaques. Although these differences could reflect cytokine-driven inflammatory events accompanying plaque instability, VEGF and VEGFR1 could be key mediators. Copyright © 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Association between plaque instability, angiogenesis and symptomatic carotid occlusive disease,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2001R. Mofidi Background: Angiogenesis is a recognized feature of the atherosclerotic process and has been described in the context of unstable coronary atherosclerotic lesions. The aim of this study was to assess the association between angiogenesis in atherosclerotic carotid plaques and microscopic features of plaque instability, in particular intraplaque haemorrhage. Methods: Consecutive patients undergoing carotid endarterectomy were included. Endarterectomy specimens were divided into their constituent atherosclerotic lesions. Histological sections were prepared and stained with haematoxylin and eosin, and immunohistochemically with an endothelial cell marker (CD34). The quantity of intraplaque haemorrhage was measured in transverse histological sections using computerized image analysis. Microvessel counts were performed in CD34-stained sections and were verified through computerized image analysis. Results: Some 239 atherosclerotic lesions from 73 patients were available for analysis; 73 were early lesions, 74 were raised fibroatheromas and 92 were unstable atherosclerotic plaques. One hundred and fifty lesions were not haemorrhagic; 89 exhibited intraplaque haemorrhage, of which 28 involved less than 50 per cent of the plaque sectional area. There were higher microvessel counts in plaques containing over 50 per cent haemorrhage (P < 0·0001), unstable atherosclerotic lesions (P < 0·0001) and atherosclerotic lesions obtained from symptomatic patients (P < 0·001). Conclusion: There are strong associations between plaque vascularity, quantity of intraplaque haemorrhage and presence of symptomatic carotid occlusive disease. © 2001 British Journal of Surgery Society Ltd [source] Differences in the detection of cyclo-oxygenase 1 and 2 proteins in symptomatic and asymptomatic carotid plaquesBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2001S. M. Wijeyaratne Background: The expression of cyclo-oxygenase (COX) 1 and 2 has been demonstrated in atherosclerotic arteries. In the present study this was correlated with symptoms arising from a carotid plaque. Methods: Carotid plaques from 12 asymptomatic patients were compared with 11 plaques from patients who had had neurological symptoms within the preceding 30 days. Sections were stained with haematoxylin and eosin, elastin van Gieson and goat antihuman antibodies to COX-1 and COX-2. Plaque morphology was correlated with neurological symptoms. The area with positive COX-1 and COX-2 staining was measured by computerized planimetry in entire cross-sections and in specific areas of the plaque. Results: There was a significant association between cap thinning and plaque rupture with symptoms (P = 0·003). The percentage area of positive staining in entire cross-sections for both COX-1 and COX-2 was significantly greater in symptomatic plaques (P = 0·001 and 0·0004 respectively). Staining in symptomatic plaques was significantly greater in the cap (COX-1: P = 0·001; COX-2: P = 0·0001) and shoulder (COX-1: P = 0·008; COX-2: P = 0·007) regions of the plaque. COX-1 expression in the sclerotic area was not increased (P = 0·15) although COX-2 staining was significantly greater (P = 0·04). Conclusion: Both COX-1 and COX-2 detection was increased in symptomatic plaques. COX may contribute to plaque rupture and the onset of symptoms. © 2001 British Journal of Surgery Society Ltd [source] | |||||||||||||||||||||||||