Surinder Dhanjil

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.

Cardiovascular Outcomes in Type 2 Diabetes: A double-blind placebo-controlled study of bezafibrate: the St. Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study

OBJECTIVE To determine whether serum lipid intervention, in addition to conventional diabetes treatment, could alter cardiovascular outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS There were 164 type 2 diabetic subjects (117 men, 47 women) without a history of clinical cardiovascular disease randomized to receive either bezafibrate or placebo daily on a double-blind basis in addition to routine diabetes treatment and followed prospectively for a minimum of 3 years. Serial biochemical and noninvasive vascular assessments, carotid and femoral artery B-mode ultrasound measurements, and those pertaining to coronary heart disease (CHD)—clinical history, the World Health Organization (WHO) cardiovascular questionnaire, and resting and exercise electrocardiogram (ECG)—were recorded. RESULTS Bezafibrate treatment was associated with significantly greater reductions over 3 years in median serum triglyceride (−32 vs. 4%, P = 0.001), total cholesterol (−7 vs. −0.3%, P = 0.004), and total−to-HDL cholesterol ratio (−12 vs. −0.0%, P = 0.001), and an increase in HDL cholesterol (6 vs. −2%, P = 0.02) as compared with placebo. There was a trend toward a greater reduction of fibrinogen (−18 vs. −6%, P = 0.08) at 3 years. No significant differences between the two groups were found in the progress of ultrasonically measured arterial disease. In those treated with bezafibrate, there was a significant reduction (P = 0.01, log-rank test) in the combined incidence of Minnesota-coded probable ischemic change on the resting ECG and of documented myocardial infarction. CONCLUSIONS Improving dyslipidemia in type 2 diabetic subjects had no effect on the progress of ultrasonically measured arterial disease, although the lower rate of “definite CHD events” in the treated group suggests that this might result in a reduction in the incidence of coronary heart disease.

Reproducibility of Computer-Quantified Carotid Plaque Echogenicity Can We Overcome the Subjectivity?

Background and Purpose We sought to assess the reproducibility, interobserver variability, and application to clinical studies of a new method for the quantitative assessment of carotid plaque echogenicity. Methods Carotid plaques were scanned with the use of ultrasound, and their images were stored in a computer. They were normalized by assigning certain gray values to blood and adventitia, and the gray scale median (GSM) was used to quantify their echogenicity. The variability between storage media, between degrees of magnification, and between probes was assessed. The method was applied to 232 asymptomatic carotid plaques causing 60% to 99% stenosis in relation to the presence of ipsilateral CT-demonstrated brain infarcts. In all parts of the study the plaque GSM was measured before and after normalization to evaluate its effect. Interobserver agreement for the scanning process was assessed. Results The GSM mean difference before and after normalization for variability studies of storage media, degrees of magnification, and probes was −14.5 and −0.12, 2.24 and 1.68, and −8.3 and −0.7, respectively. The median GSM of plaques associated with ipsilateral nonlacunar silent CT-demonstrated brain infarcts was 14, and that of plaques that were not so associated was 30 (P =0.003). The interobserver GSM difference was −0.05 (95% CI, −1.7 to 1.6). Conclusions Our method decreases the variability between storage media and between probes but not the variability between degrees of magnification. It separates echomorphologically the carotid plaques associated with silent nonlacunar CT-demonstrated brain infarcts from plaques that are not so associated.

Carotid artery wall motion estimated from b-mode ultrasound using region tracking and block matching

The motion of the carotid atheromatous plaque relative to the adjacent wall may be related to the risk of cerebral events. A quantitative method for motion estimation was applied to analyse arterial wall movement from sequences of 2-D B-mode ultrasound (US) images. Image speckle patterns were tracked between successive frames using the correlation coefficient as the matching criterion. The size of the selected region-of-interest (ROI) was shown to affect the motion analysis results; an optimal size of 3.2 x 2.5 mm(2) was suggested for tracking a region at the wall-lumen interface and of 6.3 x 2.5 mm(2) for one within the tissue. The results showed expected cyclical motion in the radial direction and some axial movement of the arterial wall. The method can be used to study further the axial motion of the carotid artery wall and plaque and, thus, provide useful insight into the mechanisms of atherosclerosis.

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.

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.

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.

Comparability of the ultrasonic tissue characteristics of carotid plaques.

Hypoechoic carotid atherosclerotic plaques on ultrasonographic examination were found to be associated with cerebrovascular events. This underlines the need for an accurate evaluation of their echotexture characteristics. The objective of this study was to further validate a proposed method of normalization aiming to facilitate the comparability of these characteristics. The sonographic examination involved imaging of carotid plaques using duplex technique and capturing, digitization, and normalization in a computer in a standard way. In the first part, the interobserver and interscanner variability and the gain‐level variability within the ultrasound unit were examined, before and after normalization, in terms of plaque echotexture. The second part investigated the effect of normalization on the echotexture of 419 symptomatic and asymptomatic plaques. Our results indicated that the normalization reduced the interscanner variability and the gain‐level variability. The interobserver variability was excellent. In addition, this process further distinguished the echotexture characteristics of symptomatic and asymptomatic carotid plaques, which encourages the use of this method in natural history studies in persons with asymptomatic carotid atherosclerotic disease, aiming to identify those at higher risk for stroke. These patients might benefit from a carotid endarterectomy.

Association between offspring birth weight and atherosclerosis in middle aged men and women: British Regional Heart Study

L ow birth weight is associated with cardiovascular disease in adulthood, but the mechanisms underlying these associations remain unclear.1 One possibility is that poor intra-uterine nutrition “programmes” adult disease.1 An alternative hypothesis is that specific polymorphisms with pleiotrophic effects result in both small birth size and cardiovascular disease risk.2 Epidemiological evidence for a genetic role in the association comes from the recent finding that offspring birth weight predicts parental cardiovascular disease risk.3,4 As an infant’s low birth weight cannot determine its own parents’ risk of cardiovascular disease through intrauterine programming, a plausible explanation for these trans-generational associations is that of a common genetic link. In this paper we investigate the associations between offspring birth weight and parental carotid intima media thickness, an indicator of pre-clinical disease. Data were used from the Dewsbury and Maidstone cohort of the British Regional Heart Study. B-mode ultrasound measurements of carotid arteries, together with a detailed physical examination, blood tests, and research nurse interview were undertaken on 375 women and 425 men, aged 56–75 years. Full details of all measurements have been …