Maura Griffin

Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women : The British Regional Heart Study

BACKGROUND AND PURPOSE B-mode ultrasound is a noninvasive method of examining the walls of peripheral arteries and provides measures of the intima-media thickness (IMT) at various sites (common carotid artery, bifurcation, internal carotid artery) and of plaques that may indicate early presymptomatic disease. The reported associations between cardiovascular risk factors, clinical disease, IMT, and plaques are inconsistent. We sought to clarify these relationships in a large, representative sample of men and women living in 2 British towns. METHODS The study was performed during 1996 in 2 towns (Dewsbury and Maidstone) of the British Regional Heart Study that have an approximately 2-fold difference in coronary heart disease risk. The male participants were drawn from the British Regional Heart Study and were recruited in 1978-1980 and form part of a national cohort study of 7735 men. A random sample of women of similar age to the men (55 to 77 years) was also selected from the age-sex register of the general practices used in the original survey. A wide range of data on social, lifestyle, and physiological factors, cardiovascular disease symptoms, and diagnoses was collected. Measures of right and left common carotid IMT (IMTcca) and bifurcation IMT (IMTbif) were made, and the arteries were examined for plaques 1.5 cm above and below the flow divider. RESULTS Totals of 425 men and 375 women were surveyed (mean age, 66 years; range, 56 to 77 years). The mean (SD) IMTcca observed were 0. 84 (0.21) and 0.75 (0.16) mm for men and women, respectively. The mean (SD) IMTbif were 1.69 (0.61) and 1.50 (0.77) mm for men and women, respectively. The correlation between IMTcca and IMTbif was similar in men (r=0.36) and women (r=0.38). There were no differences in mean IMTcca or IMTbif between the 2 towns. Carotid plaques were very common, affecting 57% (n=239) of men and 58% (n=211) of women. Severe carotid plaques with flow disturbance were rare, affecting 9 men (2%) and 6 women (1.6%). Plaques increased in prevalence with age, affecting 49% men and 39% of women aged <60 years and 65% and 75% of men and women, respectively, aged >70 years. Plaques were most common among men in Dewsbury (79% affected) and least common among men in Maidstone (34% affected). IMTcca showed a different pattern of association with cardiovascular risk factors from IMTbif and was associated with age, SBP, and FEV1 but not with social, lifestyle, or other physiological risk factors. IMTbif and carotid plaques were associated with smoking, manual social class, and plasma fibrinogen. IMTbif and carotid plaques were associated with symptoms and diagnoses of cardiovascular diseases. IMTbif associations with cardiovascular risk factors and prevalent cardiovascular disease appeared to be explained by the presence of plaques in regression models and in analyses stratified by plaque status. CONCLUSIONS IMTcca, IMTbif, and plaque are correlated with each other but show differing patterns of association with risk factors and prevalent disease. IMTcca is strongly associated with risk factors for stroke and with prevalent stroke, whereas IMTbif and plaque are more directly associated with ischemic heart disease risk factors and prevalent ischemic heart disease. Our analyses suggest that presence of plaque, rather than the thickness of IMTbif, appears to be the major criterion of high risk of disease, but confirmation of these findings in other populations and in prospective studies is required. The association of fibrinogen with plaque appears to be similar to its association with incident cardiovascular disease. Further work elucidating the composition of plaques using ultrasound imaging would be helpful, and more data, analyzed to distinguish plaque from IMTbif and IMTcca, are required to understand the significance of thicker IMT in the absence of plaque.

Carotid Plaque Echolucency Increases the Risk of Stroke in Carotid Stenting The Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) Study

Background—Carotid artery stenting (CAS) has recently emerged as a potential alternative to carotid endarterectomy. Cerebral embolization is the most devastating complication of CAS, and the echogenicity of carotid plaque has been indicated as one of the risk factors involved. This is the first study to analyze the role of a computer-assisted highly reproducible index of echogenicity, namely the gray-scale median (GSM), on the risk of stroke during CAS. Methods and Results—The Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) registry included 418 cases of CAS collected from 11 international centers. An echographic evaluation of carotid plaque with GSM measurement was made preprocedurally. The onset of neurological deficits during the procedure and the postprocedural period was recorded. The overall rate of neurological complications was 3.6%: minor strokes, 2.2%, and major stroke, 1.4%. There were 11 of 155 strokes (7.1%) in patients with GSM ≤25 and 4 of 263 (1.5%) in patients with GSM >25 (P=0.005). Patients with severe stenosis (≥85%) had a higher rate of stroke (P=0.03). The effectiveness of brain protection devices was confirmed in those with GSM >25 (P=0.01) but not in those with GSM ≤25. Multivariate analysis revealed that GSM (OR, 7.11; P=0.002) and rate of stenosis (OR, 5.76; P=0.010) are independent predictors of stroke. Conclusions—Carotid plaque echolucency, as measured by GSM ≤25, increases the risk of stroke in CAS. The inclusion of echolucency measured as GSM in the planning of any endovascular procedure of carotid lesions allows stratification of patients at different risks of complications in CAS.

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.

Angiographic and Duplex Grading of Internal Carotid Stenosis: Can We Overcome the Confusion?

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

Hemispheric symptoms and carotid plaque echomorphology.

PURPOSE In patients with carotid bifurcation disease, the risk of stroke mainly depends on the severity of the stenosis, the presenting hemispheric symptom, and, as recently suggested, on plaque echodensity. We tested the hypothesis that asymptomatic carotid plaques and plaques of patients who present with different hemispheric symptoms are related to different plaque structure in terms of echodensity and the degree of stenosis. METHODS Two hundred sixty-four patients with 295 carotid bifurcation plaques (146 symptomatic, 149 asymptomatic) causing more than 50% stenosis were examined with duplex scanning. Thirty-six plaques were associated with amaurosis fugax (AF), 68 plaques were associated with transient ischemic attacks (TIAs), and 42 plaques were associated with stroke. B-mode images were digitized and normalized using linear scaling and two reference points, blood and adventitia. The gray scale median (GSM) of blood was set to 0, and the GSM of the adventitia was set to 190 (gray scale range, black = 0; white = 255). The GSM of the plaque in the normalized image was used as the objective measurement of echodensity. RESULTS The mean GSM and the mean degree of stenosis, with 95% confidence intervals, for plaques associated with hemispheric symptoms were 13.3 (10.6 to 16) and 80.5 (78.3 to 82.7), respectively; and for asymptomatic plaques, the mean GSM and the mean degree of stenosis were 30.5 (26.2 to 34.7) and 72. 2 (69.8 to 74.5), respectively. Furthermore, in plaques related to AF, the mean GSM and the mean degree of stenosis were 7.4 (1.9 to 12. 9) and 85.6 (82 to 89.2), respectively; in those related to TIA, the mean GSM and the mean degree of stenosis were 14.9 (11.2 to 18.6) and 79.3 (76.1 to 82.4), respectively; and in those related to stroke, the mean GSM and the mean degree of stenosis were 15.8 (10.2 to 21.3) and 78.1 (73.4 to 82.8), respectively. CONCLUSION Plaques associated with hemispheric symptoms are more hypoechoic and more stenotic than those associated with no symptoms. Plaques associated with AF are more hypoechoic and more stenotic than those associated with TIA or stroke or those without symptoms. Plaques causing TIA and stroke have the same echodensity and the same degree of stenosis. These findings confirm previous suggestions that hypoechoic plaques are more likely to be symptomatic than hyperechoic ones. They support the hypothesis that the pathophysiologic mechanism for AF is different from that for TIA and stroke.

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.

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.

The objective characterisation of ultrasonic carotid plaque features.

OBJECTIVE To determine the influence of ultrasonic carotid plaque morphology on the incidence of ipsilateral hemispheric symptoms (IHS). DESIGN Cross-sectional study. MATERIALS A consecutive series of 80 patients (96 plaques) with more than 50% ICA stenosis was studied. METHODS B mode ultrasonic images were captured and transferred to a computer on magneto-optic disk and standardised using linear scaling so that adventitia would have a grey scale median (GSM) value of 185-195 and blood 0-5. The GSM and the percentage of echolucent pixels (PEP) in plaques were determined to measure echodensity. Homogeneity, entropy, and contrast were also determined to measure spatial distribution (heterogeneity) of grey shades in each plaque. Each measurement was correlated to presence or absence of IHS. RESULTS Twenty-five plaques were associated with IHS and 71 plaques were asymptomatic. In symptomatic plaques the mean of GSM was 23 and the mean of PEP was 70%, compared to 38 and 55% respectively in asymptomatic plaques (p = 0.02; Wilcoxon test). Sixty per cent of symptomatic plaques were associated with a homogeneity, entropy, and contrast values of > 0.2, < 2.95, < 150 respectively as compared to 40% in asymptomatic plaques. Multiple regression analysis revealed that the GSM and the PEP were the most significant variables (p = 0.001) that are related to presence or absence of IHS. CONCLUSION This study indicates that computer aided analysis of ultrasonic B mode features of carotid plaques could identify a potentially high-risk subgroup (patients with IHS). A GSM less than 40 or PEP greater than 50% is a good predictor of IHS related to carotid plaques. The fact that these measurements are operator independent and performed after image standardisation should encourage their use in multicenter clinical trials where different operators and equipment are used.

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.

Femoral atherosclerosis in an older British population: prevalence and risk factors.

Most estimates of the prevalence of peripheral atherosclerosis have been based on intermittent claudication or lower limb blood flow. The aim of this study was therefore to determine the prevalence of underlying femoral plaque, and to determine its association with other cardiovascular disease and risk factors. Presence of plaque was identified using ultrasound in a random sample of men (n=417) and women (n=367) aged 56-77 years. Coexistent cardiovascular disease, exercise and smoking were determined by questionnaire, blood pressure was recorded, and serum cholesterol and plasma fibrinogen were determined. Of the 784 subjects that were scanned, 502 (64%) demonstrated atherosclerotic plaque. Disease prevalence increased significantly with age (P<0.0001), and was more common in men (67.1 vs. 59.4%, P<0.05). Subjects with femoral plaque had a significantly greater odds of previous ischaemic heart disease (OR 2. 2, 95% CI 1.3, 3.7) and angina (OR 1.7, 95% CI 1.03, 2.7), but not of stroke or leg pain on exercise. Current and ex-smoking, raised serum total cholesterol and plasma fibrinogen levels, but not blood pressure, were associated with an increased risk of femoral plaque, independent of age and sex. Frequent exercise and a high HDL cholesterol were significantly associated with lower risk. In conclusion, therefore, atherosclerotic disease of the femoral artery affects almost two-thirds of the population in late middle age. It is associated with an increased prevalence of ischaemic heart disease and angina, but whether detecting at risk individuals using ultrasound offers advantages over simpler and less expensive risk factor scoring requires evaluation in trials.