Extent of vascular plaque predicts future cardiovascular events in patients with systemic lupus erythematosus.

OBJECTIVE: Patients with SLE have increased prevalence of clinical cardiovascular disease (CVD) and subclinical atherosclerosis. Although 30-40% of patients with SLE have vascular plaque on ultrasound scanning, this study is the first to consider the relationship between total burden of plaque and subsequent CVD risk. METHODS: One hundred patients with SLE and without any previous clinical CVD underwent vascular ultrasound scans of both carotid and both common femoral bifurcations between 2011 and 2013. Clinical, serological, demographic and treatment data were collected at baseline. Patients were followed till 2020 to identify those who developed new onset coronary disease or stroke. Statistical analysis to identify factors associated with increased risk of developing CVD events was carried out. RESULTS: Thirty-six patients had plaque at baseline. During follow-up five patients (all had baseline plaque) developed coronary disease and two, without baseline plaque, developed lacunar strokes. Mean (s.d.) age of these patients was 46.5 (4.5) years. Patients with three or more baseline bifurcations with plaque were 10 times more likely to develop CVD than those with 0-2 bifurcations with plaques (OR 9.9, P = 0.009). TPA > 16mm2 was associated with six-fold increased risk of CVD (OR = 6.44, P = 0.028). Patients with disease duration > 14 years were more likely than those with disease duration < 14 years to develop CVD (OR 8.3 P = 0.043). CONCLUSIONS: The number of bifurcations with plaque and TPA in patients with SLE may be valuable in assessing risk of CVD and deciding on clinical measures to reduce this risk.

Serum Metabolomic Signatures Can Predict Subclinical Atherosclerosis in Patients With Systemic Lupus Erythematosus.

[Figure: see text].

Total plaque area and plaque echogenicity are novel measures of subclinical atherosclerosis in patients with systemic lupus erythematosus.

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.

Dynamic carotid plaque imaging using ultrasonography.

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, <70°), moderately discordant (MAS, 70°-120°), and discordant (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.

Carotid Plaque-RADS: A Novel Stroke Risk Classification System.

BACKGROUND: Carotid artery atherosclerosis is highly prevalent in the general population and is a well-established risk factor for acute ischemic stroke. Although the morphological characteristics of vulnerable plaques are well recognized, there is a lack of consensus in reporting and interpreting carotid plaque features. OBJECTIVES: The aim of this paper is to establish a consistent and comprehensive approach for imaging and reporting carotid plaque by introducing the Plaque-RADS (Reporting and Data System) score. METHODS: A panel of experts recognized the necessity to develop a classification system for carotid plaque and its defining characteristics. Using a multimodality analysis approach, the Plaque-RADS categories were established through consensus, drawing on existing published reports. RESULTS: The authors present a universal classification that is applicable to both researchers and clinicians. The Plaque-RADS score offers a morphological assessment in addition to the prevailing quantitative parameter of "stenosis." The Plaque-RADS score spans from grade 1 (indicating complete absence of plaque) to grade 4 (representing complicated plaque). Accompanying visual examples are included to facilitate a clear understanding of the Plaque-RADS categories. CONCLUSIONS: Plaque-RADS is a standardized and reliable system of reporting carotid plaque composition and morphology via different imaging modalities, such as ultrasound, computed tomography, and magnetic resonance imaging. This scoring system has the potential to help in the precise identification of patients who may benefit from exclusive medical intervention and those who require alternative treatments, thereby enhancing patient care. A standardized lexicon and structured reporting promise to enhance communication between radiologists, referring clinicians, and scientists.

The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke.

OBJECTIVE: To test the hypothesis that the size of a juxtaluminal black (hypoechoic) area (JBA) in ultrasound images of asymptomatic carotid artery plaques predicts future ipsilateral ischemic stroke. METHODS: A JBA was defined as an area of pixels with a grayscale value <25 adjacent to the lumen without a visible echogenic cap after image normalization. The size of a JBA was measured in the carotid plaque images of 1121 patients with asymptomatic carotid stenosis 50% to 99% in relation to the bulb (Asymptomatic Carotid Stenosis and Risk of Stroke study); the patients were followed for up to 8 years. RESULTS: The JBA had a linear association with future stroke rate. The area under the receiver-operating characteristic curve was 0.816. Using Kaplan-Meier curves, the mean annual stroke rate was 0.4% in 706 patients with a JBA <4 mm(2), 1.4% in 171 patients with a JBA 4 to 8 mm(2), 3.2% in 46 patients with a JBA 8 to 10 mm(2), and 5% in 198 patients with a JBA >10 mm(2) (P < .001). In a Cox model with ipsilateral ischemic events (amaurosis fugax, transient ischemic attack [TIA], or stroke) as the dependent variable, the JBA (<4 mm(2), 4-8 mm(2), >8 mm(2)) was still significant after adjusting for other plaque features known to be associated with increased risk, including stenosis, grayscale median, presence of discrete white areas without acoustic shadowing indicating neovascularization, plaque area, and history of contralateral TIA or stroke. Plaque area and grayscale median were not significant. Using the significant variables (stenosis, discrete white areas without acoustic shadowing, JBA, and history of contralateral TIA or stroke), this model predicted the annual risk of stroke for each patient (range, 0.1%-10.0%). The average annual stroke risk was <1% in 734 patients, 1% to 1.9% in 94 patients, 2% to 3.9% in 134 patients, 4% to 5.9% in 125 patients, and 6% to 10% in 34 patients. CONCLUSIONS: The size of a JBA is linearly related to the risk of stroke and can be used in risk stratification models. These findings need to be confirmed in future prospective studies or in the medical arm of randomized controlled studies in the presence of optimal medical therapy. In the meantime, the JBA may be used to select asymptomatic patients at high stroke risk for carotid endarterectomy and spare patients at low risk from an unnecessary operation.

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 (OR adjusted=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 (OR adjusted=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 (OR adjusted=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.

Arterial Ultrasound Testing to Predict Atherosclerotic Cardiovascular Events.

BACKGROUND: Studies have indicated that the presence and size of subclinical atherosclerotic plaques improve the prediction of atherosclerotic cardiovascular events (ASCVE) over and above that provided by conventional risk factors alone. However, the relative contribution of different ultrasonographic measurements and sites of measurements on the 10-year ASCVD risk is largely unknown. OBJECTIVES: Our aims were to determine the relative performance of carotid intima-media thickness, plaque thickness, and plaque area in 10-year ASCVD prediction when added to conventional risk factors as well as whether the vascular territory of these measurements, carotid or common femoral bifurcation, and the number of bifurcations with plaque (NBP) influence prediction. METHODS: We enrolled 985 adults (mean age: 58.1 ± 10.2 years) free of atherosclerotic cardiovascular disease. Conventional risk factors were recorded, and both carotid and common femoral bifurcations were scanned with ultrasonography. The primary endpoint was a composite of first-time fatal or nonfatal ASCVE. RESULTS: Over a mean ± SD follow-up of 13.2 ± 3.7 years, ASCVE occurred in 154 (15.6%) participants. By adding different plaque measurements to conventional risk factors in a Cox model, net reclassification improvement was 10.4% with maximum intima-media thickness, 9.5% with carotid plaque thickness, and 14.2% with carotid plaque area. It increased to 16.1%, 16.6%, and 16.6% (P < 0.0001) by adding measurements from 4 bifurcations: NBP, total plaque thickness, and total plaque area, respectively. CONCLUSIONS: NBP, total plaque thickness, or total plaque area from both the carotid and common femoral bifurcations provides a better prediction of future ASCVE than measurements from a single site. The results need to be validated in an independent cohort.

Performance of SCORE2 and SCORE2-OP risk algorithms in a Cypriot cohort.

BACKGROUND: SCORE2 and SCORE2-OP algorithms and associated online calculators provide a new and easy method of estimating the 10-year cardiovascular risk in apparently healthy Europeans. The aim of the study was to determine the performance of these algorithms in terms of discrimination and calibration in the cohort of the Cyprus Epidemiological Study on Atherosclerosis (CESA), not only for the 10-year risk for myocardial infarction (MI), stroke and cardiovascular death, but also for all types of atherosclerotic cardiovascular events (ASCVE). METHODS: SCORE2 and SCORE2-OP for low-risk regions were calculated in a non-diabetic subset of CESA consisting of 908 people (mean age±SD: 57.8±10.5; range 40-89; 58.8% female) using baseline risk factors. Mean follow-up was 13.2±3.7 years (range 1-17) with 89 primary endpoints (MI, stroke and cardiovascular death) and 136 secondary endpoints (primary endpoints, angina, cardiac failure, coronary revascularization, transient ischemic attack, claudication and critical limb ischemia). RESULTS: The C-statistic for the prediction of the primary endpoint for all ages was 0.76 (95% CI 0.70 to 0.81) and the observed 10-year event rate was similar to the predicted one. However, the observed 10-year rate for secondary events was similar to the estimated one only when the algorithm for high-risk regions was used. CONCLUSIONS: SCORE2 and SCORE2-OP moderate risk algorithms perform well in the Cypriot population for predicting the 10-year risk for MI, stroke and fatal cardiovascular disease. However, an estimate of the 10-year risk for all ASCVD events is best calculated from the high-risk algorithm.

Carotid Ultrasound Boundary Study (CUBS): Technical considerations on an open multi-center analysis of computerized measurement systems for intima-media thickness measurement on common carotid artery longitudinal B-mode ultrasound scans.

After publishing an in-depth study that analyzed the ability of computerized methods to assist or replace human experts in obtaining carotid intima-media thickness (CIMT) measurements leading to correct therapeutic decisions, here the same consortium joined to present technical outlooks on computerized CIMT measurement systems and provide considerations for the community regarding the development and comparison of these methods, including considerations to encourage the standardization of computerized CIMT measurements and results presentation. A multi-center database of 500 images was collected, upon which three manual segmentations and seven computerized methods were employed to measure the CIMT, including traditional methods based on dynamic programming, deformable models, the first order absolute moment, anisotropic Gaussian derivative filters and deep learning-based image processing approaches based on U-Net convolutional neural networks. An inter- and intra-analyst variability analysis was conducted and segmentation results were analyzed by dividing the database based on carotid morphology, image signal-to-noise ratio, and research center. The computerized methods obtained CIMT absolute bias results that were comparable with studies in literature and they generally were similar and often better than the observed inter- and intra-analyst variability. Several computerized methods showed promising segmentation results, including one deep learning method (CIMT absolute bias = 106 ± 89 µm vs. 160 ± 140 µm intra-analyst variability) and three other traditional image processing methods (CIMT absolute bias = 139 ± 119 µm, 143 ± 118 µm and 139 ± 136 µm). The entire database used has been made publicly available for the community to facilitate future studies and to encourage an open comparison and technical analysis (https://doi.org/10.17632/m7ndn58sv6.1).

Effect of computer monitor brightness on visual (subjective) carotid plaque characterization.

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.

Association of Intima-Media Texture With Prevalence of Clinical Cardiovascular Disease.

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.

Carotid Ultrasound Boundary Study (CUBS): An Open Multicenter Analysis of Computerized Intima-Media Thickness Measurement Systems and Their Clinical Impact.

Common carotid intima-media thickness (CIMT) is a commonly used marker for atherosclerosis and is often computed in carotid ultrasound images. An analysis of different computerized techniques for CIMT measurement and their clinical impacts on the same patient data set is lacking. Here we compared and assessed five computerized CIMT algorithms against three expert analysts' manual measurements on a data set of 1088 patients from two centers. Inter- and intra-observer variability was assessed, and the computerized CIMT values were compared with those manually obtained. The CIMT measurements were used to assess the correlation with clinical parameters, cardiovascular event prediction through a generalized linear model and the Kaplan-Meier hazard ratio. CIMT measurements obtained with a skilled analyst's segmentation and the computerized segmentation were comparable in statistical analyses, suggesting they can be used interchangeably for CIMT quantification and clinical outcome investigation. To facilitate future studies, the entire data set used is made publicly available for the community at http://dx.doi.org/10.17632/fpv535fss7.1.

Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification.

BACKGROUND: The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery (ICA) stenosis. METHODS: This was a prospective, multicenter, cohort study of patients undergoing medical intervention for vascular disease. Hazard ratios for ICA stenosis, clinical features, and plaque texture features associated with ipsilateral cerebrovascular or retinal ischemic (CORI) events were calculated using proportional hazards models. RESULTS: A total of 1121 patients with 50% to 99% asymptomatic ICA stenosis in relation to the bulb (European Carotid Surgery Trial [ECST] method) were followed-up for 6 to 96 months (mean, 48). A total of 130 ipsilateral CORI events occurred. Severity of stenosis, age, systolic blood pressure, increased serum creatinine, smoking history of more than 10 pack-years, history of contralateral transient ischemic attacks (TIAs) or stroke, low grayscale median (GSM), increased plaque area, plaque types 1, 2, and 3, and the presence of discrete white areas (DWAs) without acoustic shadowing were associated with increased risk. Receiver operating characteristic (ROC) curves were constructed for predicted risk versus observed CORI events as a measure of model validity. The areas under the ROC curves for a model of stenosis alone, a model of stenosis combined with clinical features and a model of stenosis combined with clinical, and plaque features were 0.59 (95% confidence interval [CI] 0.54-0.64), 0.66 (0.62-0.72), and 0.82 (0.78-0.86), respectively. In the last model, stenosis, history of contralateral TIAs or stroke, GSM, plaque area, and DWAs were independent predictors of ipsilateral CORI events. Combinations of these could stratify patients into different levels of risk for ipsilateral CORI and stroke, with predicted risk close to observed risk. Of the 923 patients with ≥ 70% stenosis, the predicted cumulative 5-year stroke rate was <5% in 495, 5% to 9.9% in 202, 10% to 19.9% in 142, and ≥ 20% in 84 patients. CONCLUSION: Cerebrovascular risk stratification is possible using a combination of clinical and ultrasonic plaque features. These findings need to be validated in additional prospective studies of patients receiving optimal medical intervention alone.

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= 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.

Silent embolic infarcts on computed tomography brain scans and risk of ipsilateral hemispheric events in patients with asymptomatic internal carotid artery stenosis.

OBJECTIVES: This study tested the hypothesis that silent embolic infarcts on computed tomography (CT) brain scans can predict ipsilateral neurologic hemispheric events and stroke in patients with asymptomatic internal carotid artery stenosis. METHODS: In a prospective multicenter natural history study, 821 patients with asymptomatic carotid stenosis graded with duplex scanning who had CT brain scans were monitored every 6 months for a maximum of 8 years. Duplex scans were reported centrally, and stenosis was expressed as a percentage in relation to the normal distal internal carotid criteria used by the North American Symptomatic Carotid Endarterectomy Trialists. CT brain scans were reported centrally by a neuroradiologist. In 146 patients (17.8%), 8 large cortical, 15 small cortical, 72 discrete subcortical, and 51 basal ganglia ipsilateral infarcts were present; these were considered likely to be embolic and were classified as such. Other infarct types, lacunes (n = 15), watershed (n = 9), and the presence of diffuse white matter changes (n = 95) were not considered to be embolic. RESULTS: During a mean follow-up of 44.6 months (range, 6 months-8 years), 102 ipsilateral hemispheric neurologic events (amaurosis fugax in 16, 38 transient ischemic attacks [TIAs], and 47 strokes) occurred, 138 patients died, and 24 were lost to follow-up. In 462 patients with 60% to 99% stenosis, the cumulative event-free rate at 8 years was 0.81 (2.4% annual event rate) when embolic infarcts were absent and 0.63 (4.6% annual event rate) when present (log-rank P = .032). In 359 patients with <60% stenosis, embolic infarcts were not associated with increased risk (log-rank P = .65). In patients with 60% to 99% stenosis, the cumulative stroke-free rate was 0.92 (1.0% annual stroke rate) when embolic infarcts were absent and 0.71 (3.6% annual stroke rate) when present (log-rank P = .002). In the subgroup of 216 with moderate 60% to 79% stenosis, the cumulative TIA or stroke-free rate in the absence and presence of embolic infarcts was 0.90 (1.3% annual rate) and 0.65 (4.4% annual rate), respectively (log-rank P = .005). CONCLUSION: The presence of silent embolic infarcts can identify a high-risk group for ipsilateral hemispheric neurologic events and stroke and may prove useful in the management of patients with moderate asymptomatic carotid stenosis.

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.

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.

Measurement of blood flow in the deep veins of the lower limb using the geko™ neuromuscular electro-stimulation device.

BACKGROUND: A previous study using electrical stimulation of the common peroneal nerve (geko™) to activate the venous muscle pump measured blood flow in both the femoral and popliteal veins. Increased blood flow by as much as 60% was demonstrated in the femoral vein. Such an increase is assumed to be as a result of an increase in venous flow from the deep calf veins; however this has yet to be confirmed. The aim of this study was to conduct direct measurements in these deep calf veins to confirm this assumption in healthy individuals. METHODS: This was a single centre open-label intra-subject healthy volunteer comparison of blood flow in the peroneal, posterior tibial and gastrocnemial veins with and without the geko™ device. The device was applied to 18 volunteers. Peak venous velocity (PV) and ejected volume per individual stimulus (VS) and volume flow (VF) was determined using ultrasound. RESULTS: Peak velocity (PV) increased 216% in the peroneal vein, by 112% in the posterior tibial vein and by 137% in the gastrocnemial vein (P<0.001). Ejected volume per stimulus increased by 113% in the peroneal vein, by 38% in the posterior tibial vein and by 50% in the gastrocnemial vein (P<0.003). Associated volume flows during the muscle contraction were increased by 36%, 25% and 17%, respectively (P=0.05) CONCLUSIONS: This is the first time that neuromuscular electro-stimulation has been shown to be an effective method of increasing flow in the axial deep veins of the calf. Significant increases in velocity and volume flow in response to the electrical stimulus were seen in all three veins studied. Enhancements of both blood velocity and volume flow are key factors in the prevention of venous stasis and ultimately deep vein thrombosis (DVT). Further studies are justified to determine the efficacy of the device in the prevention of DVT.