Niki Georgiou

Effect of Image Normalization on Carotid Plaque Classification and the Risk of Ipsilateral Hemispheric Ischemic Events: Results from the Asymptomatic Carotid Stenosis and Risk of Stroke Study:

The aim of this study was to determine the effect of image normalization on plaque classification and the risk of ipsilateral ischemic neurologic events in patients with asymptomatic carotid stenosis. The first 1,115 patients recruited to the Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study with a follow-up of 6 to 84 months (mean 37.1 months) were included in this study. Duplex ultrasonography was used for grading the degree of internal carotid artery stenosis and for plaque characterization (types 1–5), which was performed before and after image normalization. One hundred sixteen ipsilateral ischemic hemispheric events occurred. Image normalization resulted in 60% of plaques being reclassified. Before image normalization, a high event rate was associated with all types of plaque. After image normalization, 109 (94%) of the events occurred in patients with plaque types 1 to 3. For patients with European Carotid Stenosis Trial (ECST) 70 to 99% diameter stenosis (equivalent to North American Symptomatic Carotid Endarterectomy Trial [NASCET] 50–99%) with plaque types 1 to 3, the cumulative stroke rate was 14% at 7 years (2% per year), and for patients with plaque types 4 and 5, the cumulative stroke rate was 0.9% at 7 years (0.14% per year). The results suggest that asymptomatic patients with plaque types 4 and 5 classified as such after image normalization are at low risk irrespective of the degree of stenosis.

Breastfeeding and Atherosclerosis Intima-Media Thickness and Plaques at 65-Year Follow-Up of the Boyd Orr Cohort

Objectives—The impact of breastfeeding in infancy on cardiovascular disease risk is uncertain. We related breastfeeding in infancy to atherosclerosis in adulthood. Methods and Results—A historic cohort study based on a 65-year follow-up of the Carnegie (Boyd Orr) survey of diet and health in prewar Britain, 1937 to 1939. A total of 732 eligible cohort members living in or around Aberdeen, Bristol, Dundee, Wisbech, and London were invited for follow-up examinations in 2002, and 405 (55%) participated. In models controlling for age and sex, breastfeeding was inversely associated with common carotid intima-media thickness (IMT; difference −0.03 mm; 95% CI, −0.07 to 0.01), bifurcation IMT (difference −0.19 mm; 95% CI, −0.37 to −0.01), carotid plaque (odds ratio [OR], 0.52; 95% CI, 0.29 to 0.92), and femoral plaque (OR, 0.54; 95% CI, 0.26 to 1.12), compared with bottle-feeding. Controlling for socioeconomic variables in childhood and adulthood, smoking and alcohol made little difference to effect estimates. Controlling for factors potentially on the causal pathway (blood pressure, adiposity, cholesterol, insulin resistance, and C-reactive protein) made little difference to observed associations. Conclusions—Breastfeeding may be associated with a reduced risk of atherosclerosis in later life. Measurement error and power considerations limit the extent to which conclusions about the mechanisms underlying this relationship can be made.

Juxtaluminal hypoechoic area in ultrasonic images of carotid plaques and hemispheric symptoms

OBJECTIVES The aim was to determine the diagnostic value of a juxtaluminal black (hypoechoic) area without a visible echogenic cap (JBA) in ultrasonic images of internal carotid artery plaques. METHODS Ultrasonic images of plaques from 324 patients with asymptomatic (n = 139) and symptomatic (n = 185) internal carotid 50% to 99% stenosis in relation to the bulb (European Carotid Surgery Trial) referred for duplex scanning were studied. The JBA in mm(2) and the gray-scale median (GSM) were obtained after image normalization. Cut-off points for GSM and JBA (combined highest sensitivity with highest specificity) were determined from receiver operator characteristic (ROC) curves. RESULTS JBA >or= 8 mm(2) was associated with a high prevalence of symptomatic plaques in all grades of stenosis. In a multiple logistic regression model, increasing stenosis (mild, moderate, severe), GSM <or= 15 and JBA >or= 8 mm(2) were independent predictors of the presence of hemispheric symptoms. This model could identify a high-risk group of 188 plaques that contained 142 (77%) of the 185 symptomatic plaques (odds ratio [OR], 6.7; 95% confidence interval [CI], 4.08-10.91), (P < .001), (sensitivity: 77%; specificity 66%; positive predictive value 75%; negative predictive value 68%). CONCLUSIONS The results of this study indicate the diagnostic value and for the first time suggest a cut-off point of 8 mm(2) for JBA. This cut-off point needs to be validated in other groups and then applied to prospective studies of asymptomatic patients.

Leukocyte telomere length is associated with measures of subclinical atherosclerosis

AIMS Our aim was to test the association of mean leukocyte telomere length (LTL) with ultrasonic measures of subclinical atherosclerosis such as intima-media thickness in the common carotid (IMTcc) and sum of plaque areas (SPA) and with serological markers. METHODS AND RESULTS Carotid and femoral bifurcations were scanned in 762 general population volunteers (46% men) over 40. Four features were considered: (a) IMTcc, (b) sum plaque areas of carotid plaques (SPAcar), (c) sum plaque area of common femoral plaques (SPAfem) and (d) sum plaque area (SPA--sum of the plaque areas of the largest plaques present in each of both carotid and femoral bifurcations). Mean LTL was determined with a quantitative real-time PCR-based method. IMTcc was strongly associated with mean LTL both before and after correction for traditional risk factors (B=-0.002; 95% CI=-0.004 to -0.00; p=0.014). In sex-specific analysis, the association was stronger in men (p for sex interaction<0.001). SPAfem was associated with LTL in women before and after correction (B=-0.195; 95% CI=-0.38 to -0.01; p=0.037) (p for sex interaction<0.001). LTL was also associated with age and sex-adjusted levels of hsCRP (p=0.012), sCD40L (p=0.042), homocysteine (p=0.006), creatinine (p=0.02), ApoA1 (p=0.01), Lp(a) (p=0.04) and HOMA-IR (p=0.008). CONCLUSIONS Our results support the telomere hypothesis and highlight potential differences in the biological mechanisms leading to intima-media thickening and/or plaque formation between vascular beds. They may provide insights into a novel treatment of antisenescence to prevent atherosclerosis.

Associations of insulin-Like growth factor (IGF)-I, IGF-II, IGF binding protein (IGFBP)-2 and IGFBP-3 with ultrasound measures of atherosclerosis and plaque stability in an older adult population

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.

Carotid and femoral arterial wall changes and the prevalence of clinical cardiovascular disease

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.

Association of genotypes at the matrix metalloproteinase (MMP) loci with carotid IMT and presence of carotid and femoral atherosclerotic plaques

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; p<0.001) and the MMP7 -181A allele was associated with the presence of femoral plaques (ORadjusted=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.

Media Thickness Measurement of the Common Carotid Artery

The intima-media thickness (IMT) of the common carotid artery (CCA) is widely used as an early indicator of the development of cardiovascular disease (CVD). It was proposed but not thoroughly investigated that the media thickness (MT), its composition and texture may be indicative for identifying the risk of stroke and differentiating between patients with high and low risk. In this study we present an automated method for segmentation of the media layer and measurement of its thickness in ultrasound images of the CCA. The snakes segmentation method was used, and was evaluated on 100 images against manual segmentation. The mean plusmn standard deviation (sd) for the manual and the automated IMT measurements were 0.71+0.17 mm and 0.67plusmn0.12 mm, and for the manual and the automated MT measurements were 0.25plusmn0.12 mm and 0.25plusmn0.11 mm respectively. There was no significant difference between the manual and the automated measurements. Further research for validating the proposed technique is required and for evaluating it in a larger sample of subjects.

Ultrasonic Characterization of Carotid Plaques

The multidisciplinary approach combining angiography, high-resolution ultrasound, thrombolytic therapy, plaque pathology, histochemistry, coagulation studies, and more recently molecular biology has led to the realization that carotid plaque rupture is a key mechanism underlying the development of cerebrovascular events.1, 2, 3

Texture analysis of the media-layer of the left and right common carotid artery

The intima-media thickness (IMT) of the common carotid artery (CCA) is a well-known indicator of cardiovascular disease (CVD). The objective of this study was to investigate the application of texture analysis of the medial layer (ML) of the CCA, and how texture features vary between the left and right carotid sides, as well as how these are affected by CVD. The study was performed on 200 longitudinal-section ultrasound images from 150 normal subjects, and 50 symptomatic subjects suffering with CVD. The ML was segmented automatically by a snakes segmentation system and 61 different texture features were extracted. This study showed that only the gray level difference statistics (GLDS) correlation measure of the ML component could be used to differentiate between normal subjects, and subjects suffering with CVD for either the left or the right CCA sides. We furthermore found that a number of texture features were significantly different between the left and the right CCA sides. We have found no other studies in the literature where these findings could be compared to. These findings should be further validated on a larger number of subjects as well as combined with additional risk factors.