Ultrasound assessment of carotid atherosclerosis focusing on plaque characteristics and changes over time

In a clinical perspective better methods to identify subjects at increased cardiovascular risk are needed. Atherosclerotic plaques of the carotid arteries with low echogenicity have been related to future clinical events. However, better methods to assess plaque characteristics are needed as well as more information on the variability and change over time of echogenicity in relation to occurrence and total area of non-stenotic carotid plaques. The aims were to develop a new method for plaque assessment, study variability over time and to examine plaque characteristics in relation to diabetes mellitus and hsCRP. A population sample of 64-year-old Caucasian women (n=638) with varying degrees of glucose tolerance underwent assessment of cardiovascular risk factors and bilateral ultrasound of the carotid arteries for measurement of intima-media thickness (IMT), plaque burden and plaque echogenicity, at baseline and at 6 year follow-up. A semi-automated method to evaluate echogenicity (SAMEE) and its main feature, Percentage White (PW) were developed with the visual Gray-Weale classification as reference method. PW was then also analysed in images from the follow-up examination. The SAMEE program and its main feature, Percentage White (PW), was constructed and validated to handle different technical and artifact-related sources of variability. We showed that PW is highly reproducible and correlates to a higher extent than GSM with a number of cardiovascular risk factors. Our results suggest that the problem of multiple plaques in individual subjects in our data set is best managed by measuring the average PW of all plaques. Plaque area increased as expected during 6 years of follow-up, but this was not accompanied by a change in echogenicity. Diabetes was associated with increased plaque burden and plaque echolucency at baseline. Risk factor intervention and new medication may have impacted the findings at follow-up. hsCRP≥2mg/ml as a risk marker of future cardiovascular disease was associated with carotid bulb IMT and total plaque area among women with carotid plaques. Taken together, the SAMEE program and measurement of PW may be potentially valuable tools in the identification of subjects at increased cardiovascular risk. This has to be investigated in future studies

Circulating Autoantibodies against the Apolipoprotein B-100 Peptides p45 and p210 in Relation to the Occurrence of Carotid Plaques in 64-Year-Old Women.

Immune responses against oxidized low density lipoprotein (LDL) play a key role in atherosclerosis. Previous studies have indicated inverse associations between autoantibodies to epitopes in oxidized LDL and cardiovascular disease. In this study we investigated the associations between autoantibodies against the apolipoprotein B-100 (apoB-100) peptides p45 and p210 and occurrence of carotid plaques

Percentage White: A New Feature for Ultrasound Classification of Plaque Echogenicity in Carotid Artery Atherosclerosis.

Atherosclerotic stenotic and nonstenotic plaques of the carotid artery with low echogenicity have been shown to be associated with cardiovascular disease. The aim was to develop a new method for semiautomated ultrasound image analysis to classify nonstenotic carotid plaques, evaluate cases with multiple plaques and examine the association between a new image analysis feature of echogenicity and predictors of cardiovascular disease. The new image analysis feature, percentage white (PW), represents the fraction of bright structures inside a plaque and is integrated in an objective semiautomated method to evaluate echogenicity (SAMEE) in carotid plaques. PW was constructed to take into account overall echogenicity of the image as well as noise surrounding the plaque. Consecutive ultrasound examinations of carotid plaques from a population-based screening of 64-year-old women with varying risk for cardiovascular disease were selected for the present project; 92 far-wall and 47 near-wall plaques were used as a training dataset to develop the SAMEE algorithm with visual classification according to Gray-Weale as reference; 273 plaques were used to validate the method. All plaques were included in an analysis relating predictors of cardiovascular to average PW in all plaques, PW in the biggest plaque and to the plaque with lowest PW in each subject, respectively. In the training dataset the intermethodological variability between SAMEE and visual classification showed a kappa of 0.78 and a sensitivity and specificity of 96% and 81%, respectively. In the validation set, SAMEE and visual classification showed a kappa of 0.77, a sensitivity of 96% and a specificity of 80%. The reproducibility of PW was high, evidenced by r = 0.96 and CV = 9.85% at repeated examinations. Average PW values were associated with several predictors of cardiovascular risk: lipoprotein (a), HbA1c, blood glucose, apolipoproteinB/apolipoproteinA-I; and associated negatively with the levels of adiponectin and apolipoprotein A-I. In conclusion, PW integrated within a SAMEE is a new feature for assessment of echogenicity in carotid plaques and shows excellent reproducibility and agreement with visual assessment

Percentage White: A New Feature for Ultrasound Classification of Plaque Echogenicity in Carotid Artery Atherosclerosis.

Atherosclerotic stenotic and nonstenotic plaques of the carotid artery with low echogenicity have been shown to be associated with cardiovascular disease. The aim was to develop a new method for semiautomated ultrasound image analysis to classify nonstenotic carotid plaques, evaluate cases with multiple plaques and examine the association between a new image analysis feature of echogenicity and predictors of cardiovascular disease. The new image analysis feature, percentage white (PW), represents the fraction of bright structures inside a plaque and is integrated in an objective semiautomated method to evaluate echogenicity (SAMEE) in carotid plaques. PW was constructed to take into account overall echogenicity of the image as well as noise surrounding the plaque. Consecutive ultrasound examinations of carotid plaques from a population-based screening of 64-year-old women with varying risk for cardiovascular disease were selected for the present project; 92 far-wall and 47 near-wall plaques were used as a training dataset to develop the SAMEE algorithm with visual classification according to Gray-Weale as reference; 273 plaques were used to validate the method. All plaques were included in an analysis relating predictors of cardiovascular to average PW in all plaques, PW in the biggest plaque and to the plaque with lowest PW in each subject, respectively. In the training dataset the intermethodological variability between SAMEE and visual classification showed a kappa of 0.78 and a sensitivity and specificity of 96% and 81%, respectively. In the validation set, SAMEE and visual classification showed a kappa of 0.77, a sensitivity of 96% and a specificity of 80%. The reproducibility of PW was high, evidenced by r = 0.96 and CV = 9.85% at repeated examinations. Average PW values were associated with several predictors of cardiovascular risk: lipoprotein (a), HbA1c, blood glucose, apolipoproteinB/apolipoproteinA-I; and associated negatively with the levels of adiponectin and apolipoprotein A-I. In conclusion, PW integrated within a SAMEE is a new feature for assessment of echogenicity in carotid plaques and shows excellent reproducibility and agreement with visual assessment

The association between autonomic dysfunction, inflammation and atherosclerosis in men under investigation for carotid plaques

Background Autonomic dysfunction is a risk factor for cardiovascular disease (CVD), however, the exact mechanism linking autonomic dysfunction to cardiovascular disease is not known. In this study we hypothesized that autonomic dysfunction increases inflammation, which subsequently accelerates atherosclerosis. The aim of the current study was to investigate the association between autonomic tone, inflammation and atherosclerosis. 124 men under investigation for carotid atherosclerosis were examined for autonomic function (heart rate variability; HRV and baroreflex sensitivity; BRS), inflammatory markers (white blood cell count; WBCC and C-reactive protein; CRP) and degree of carotid atherosclerosis. The direct or indirect associations between autonomic function, inflammatory parameters and carotid plaque area were investigated with multiple linear regressions. Male subjects with prevalent CVD showed larger carotid plaque area, higher WBCC, and reduced BRS compared to subjects with no history of CVD. Further, BRS was inversely associated with carotid plaque area (r = -0.21, p = 0.018) as well as inflammatory parameters WBCC and CRP (r = -0.29, p = 0.001, and r = -0.23, p = 0.009, respectively), whereas HRV only was inversely associated with WBCC (r = -0.22, p = 0.014). To investigate if inflammation could provide a link between autonomic function and carotid atherosclerosis we adjusted the associations accordingly. After adjusting for WBCC and CRP the inverse association between BRS and carotid plaque area was attenuated and did not remain significant, while both WBCC and CRP remained significantly associated with carotid plaque area, indicating that low-grade inflammation can possibly link BRS to atherosclerosis. Also, after adjusting for age, antihypertensive treatment and cardiovascular risk factors, BRS was independently inversely associated with both WBCC and CRP, and HRV independently inversely associated with WBCC. WBCC was the only inflammatory marker independently associated with carotid plaque area after adjustment. We demonstrate that autonomic dysfunction is associated with atherosclerosis and that inflammation could play an important role in mediating this relationship

Autoantibodies to the apoB-100 peptides p45 and p210 in 64-year-old women with diabetes, impaired (IGT) and normal (NGT) glucose tolerance.

<p>Ab, antibodies; Values given as absorbance units at 405 nm; Values are median (IQR).</p><p>Autoantibodies to the apoB-100 peptides p45 and p210 in 64-year-old women with diabetes, impaired (IGT) and normal (NGT) glucose tolerance.</p

Relation between IgM MDA-p210 autoantibody levels and presence of carotid plaques.

<p>The figure shows the proportion of 64-year-old women with prevalent atherosclerotic plaques in the carotid arteries in each tertile of serum concentrations of IgM MDA-p210 autoantibodies. Chi-square test was used for comparison between groups. Abs units, absorbance units at 405 nm.</p

Characteristics of 64-year old women in relation to occurrence of plaques in the carotid arteries.

<p>BMI, body mass index; BP, blood pressure; IGT, impaired glucose tolerance.</p><p>*p<0.05</p><p>**p<0.01</p><p>***p<0.001</p><p>Characteristics of 64-year old women in relation to occurrence of plaques in the carotid arteries.</p

Autoantibodies to the apoB-100 peptides p45 and p210 in 64-year-old women in relation to occurrence of atherosclerotic plaques in the carotid arteries.

<p>Ab, antibodies; Values given as absorbance units at 405 nm; Values are median (IQR)</p><p>**<i>P</i> = 0.009</p><p>Autoantibodies to the apoB-100 peptides p45 and p210 in 64-year-old women in relation to occurrence of atherosclerotic plaques in the carotid arteries.</p

Relationships between parameters for autonomic function, inflammatory markers, atherosclerosis and clinical factors.

<p>Relationships between parameters for autonomic function, inflammatory markers, atherosclerosis and clinical factors.</p