Methodological considerations of ultrasound measurement of carotid artery intima-media thickness and lumen diameter

BACKGROUND: With an increasing number of randomized studies investigating the anti-atherosclerotic effects of different preventive measures utilizing ultrasound evaluation of intima-media thickness of the carotid artery as the primary endpoint, it is of interest to critically evaluate the validity of these measurements. METHODS AND RESULTS: Small structures, the dimensions of which are far beyond the resolution limits of the equipment, may produce an ultrasound echo. Thus the very thin interface between two fluids such as oil and water will produce an echo that is much thicker than the interface itself, which is infinitely thin. Thus, the thickness of any echo defining an interface is of no anatomical interest. The thickness of an anatomical entity, such as the intima-media complex, is always defined as the distance between the leading edges of two different echoes. In spite of the similarity of the near and far wall images the thickness of the intima-media complex can only be measured in a valid way in the far wall position. CONCLUSIONS: We conclude that main outcome variables in ultrasound studies of atherosclerosis should be from the far wall. It would seem advisable to focus on far wall common carotid artery and carotid artery bulb recordings. It is likely that including near wall measurements and measurements from the internal carotid artery will decrease measurement precision and lead to increases in sample size in scientific studies; or even dilute positive results in an otherwise well designed study.     

Ultrasound measurements of carotid intima–media thickness by two semi‐automated analysis systems

Increased carotid intima–media thickness (cIMT) is associated with an increased risk of cardiac events and stroke. Several semi‐automated edge‐detection techniques for measuring cIMT are used for research and in clinical practice. Our aim was to compare two currently available semi‐automated techniques for the measurement of cIMT. Carotid ultrasound recordings were obtained from 99 subjects (mean age 54·4 ± 8·9 years, range 33–69) without known cardiovascular diseases using a General Electric (GE) Vivid 7 ultrasound scanner, 8‐MHz transducer. The far‐wall cIMT was evaluated 1–2 cm proximal to the carotid bulb. Three diastolic images (ECG R‐wave) from the left and three images from the right common carotid arteries were analysed using GE and Artery Measurement System (AMS) semi‐automated softwares. Mean systolic and diastolic blood pressures were 120 ± 13 and 76 ± 8 mmHg, respectively. The cIMT_mean (left + right)/2 by GE and cIMT_mean (left + right)/2 AMS were highly correlated (r = 0·92, P<0·001). Higher values were measured by GE (0·72 ± 0·12 mm) compared with AMS (0·69 ± 0·12 mm), and this was significant (P<0·001). The coefficients of variation for the intra‐observer variability of cIMT_mean (left + right)/2 were 1·0% (GE) and 2·2% (AMS). cIMT_mean measured by GE's semi‐automated edge‐detection method correlated well with that measured by AMS. However, there were small but significant systematic differences between the cIMT_mean values measured by the two techniques. Thus, the use of only one type of measurement program seems favourable in follow‐up studies and when evaluating treatment effects.     

Factor VIII deficiency does not protect against atherosclerosis

See also Makris M, van Veen JJ. Reduced cardiovascular mortality in hemophilia despite normal atherosclerotic load. This issue, pp 20–2; Zwiers M, Lefrandt JD, Mulder DJ, Smit AJ, Gans ROB, Vliegenthart R, Brands‐Nijenhuis AVM, Kluin‐Nelemans JC, Meijer K. Coronary artery calcification score and carotid intima–media thickness in patients with hemophilia. This issue, pp 23–9. Summary. Background: Hemophilia A patients have a lower cardiovascular mortality rate than the general population. Whether this protection is caused by hypocoagulability or decreased atherogenesis is unclear. Objectives: To evaluate atherosclerosis and endothelial function in hemophilia A patients with and without obesity as well as in matched, unaffected controls. Methods: Fifty‐one obese (body mass index [BMI] ≥ 30 kg m^?2) and 47 non‐obese (BMI ≤ 25 kg m^?2) hemophilia A patients, and 42 obese and 50 matched non‐obese male controls were included. Carotid and femoral intima–media thickness [IMT] and brachial flow‐mediated dilatation (FMD) were measured as markers of atherogenesis and endothelial function. Results: The overall population age was 50 ± 13 years. Carotid IMT was increased in obese subjects (0.77 ± 0.22 mm) as compared with non‐obese subjects (0.69 ± 0.16 mm) [mean difference 0.07 mm (95% confidence interval [CI] 0.02–0.13, P = 0.008)]. No differences in mean carotid and femoral IMT between obese hemophilic patients and obese controls were found (mean difference of 0.02 mm [95% CI ? 0.07–0.11, P = 0.67], and mean difference of 0.06 mm [95% CI ? 0.13–0.25, P = 0.55], respectively). Thirty‐five per cent of the obese hemophilic patients and 29% of the obese controls had an atherosclerotic plaque (P = 0.49), irrespective of the severity of hemophilia. Brachial FMD was comparable between obese hemophilic patients and obese controls (4.84% ± 3.24% and 5.32% ± 2.37%, P = 0.45). Conclusion: Hemophilia A patients with obesity develop atherosclerosis to a similar extent as the general male population. Detection and treatment of cardiovascular risk factors in hemophilic patients is equally necessary.     

Measurement of pulse wave velocity using pulse wave Doppler ultrasound: comparison with arterial tonometry

Pulse wave velocity (PWV), the speed of propagation of arterial pressure waves through the arterial tree, is related to arterial stiffness and is an important prognostic marker for cardiovascular events. In clinical practice PWV is commonly determined by arterial tonometry, with a noninvasive pressure sensor applied sequentially over carotid and femoral arteries. The electrocardiogram (ECG) is used as a timing reference to determine the time delay or "transit time" between the upstroke of carotid and femoral pulse waveforms. Commercially available vascular ultrasound scanners provide a pulsed wave (PW) Doppler velocity signal, which should allow determination of carotid-femoral transit time and hence PWV. We compared carotid-femoral PWV measured by tonometry and by PW Doppler ultrasound (Seimens, Apsen scanner with 7 MHz linear transducer) in asymptomatic subjects (n = 62, 26 male, aged 21 to 72 y). To test for intra-subject and inter-observer variation, ten subjects were scanned by one observer on two occasions 2 wk apart and by two observers on same day. PWV by tonometry ranged from 5.3 to 15.0 m/s. There was no significant difference between mean values of PWV obtained by the two techniques (mean difference: 0.3 m/s, standard deviation of difference: 1.5 m/s), which were closely correlated (r = 0.83). The coefficient of variation for repeated measures on the same subject by the same observer was 10.1% and the inter-observer coefficient of variation was 5.8%. These results suggest a commercial ultrasound scanner can be used to measure PWV, giving results that are reproducible and closely correlated with those obtained by arterial tonometry. (E-mail: ben_yu.jiang@kcl.ac.uk).     

Obese children show increased intimal wall thickness and decreased pulse wave velocity

Objective: Childhood obesity confers an increased risk of vascular changes and adult cardiovascular disease. Using a high‐resolution ultrasound technique that enables separation of intimal and medial layers, we examined the intimal thickness (IT) and intimal–medial thickness (IMT) of radial (RA) and dorsal pedal (DPA) arteries and the pulse wave velocity (PWV) in overweight/obese children and adolescents and in healthy subjects. Methods and results: IT and IMT of RA and DPA and PWV were measured in 33 obese children and adolescents (13·9 ± 1·6 years) and in 18 matched lean controls (14·3 ± 2·2). Increased RA IT was found in the obese group, whereas no differences in RA IMT or medial thickness were observed. Obese females accounted for the entire difference in RA IT (P = 0·04). DPA IT was inversely correlated with HDL cholesterol in the obese group (?0·56, P = 0·0089). PWV was lower in the obese group than in the lean group (6·2 ± 0·8 versus 7·0 ± 0·9 m s^?1, respectively; P = 0·001). Conclusions: Obese children and adolescents, primarily females, present with increased RA IT. The decreased PWV in the obese versus lean subjects might reflect general vasodilatation.     

Coronary artery calcification score and carotid intima–media thickness in patients with hemophilia

See also Makris M, van Veen JJ. Reduced cardiovascular mortality in hemophilia despite normal atherosclerotic load. This issue, pp 20–2; Biere‐Rafi S, Tuinenburg A, Haak BW, Peters M, Huijgen R, de Groot E, Verhamme P, Peerlinck K, Visseren FLJ, Kruip MJHA, Laros‐van Gorkom BAP, Gerdes VEA, Buller HR, Schutgens REG, Kamphuisen PW. Factor VIII deficiency does not protect against atherosclerosis. This issue, pp 30–7. Summary. Background/objectives: The traditional view that patients with hemophilia are protected against cardiovascular disease is under debate. The aim of the present study was to evaluate the presence and extent of atherosclerosis by coronary artery calcification score (CACS) and carotid intima media thickness (IMT) in patients with hemophilia, and to evaluate their cardiovascular risk profile. Methods: Sixty‐nine patients (51 with hemophilia A; 18 with hemophilia B) were studied [median age: 52 years (interquartile range [IQR] 43–64)]. Cardiovascular risk factors and prior major adverse cardiovascular events (MACEs) were recorded. CACS was derived from electron‐beam or dual‐source computed tomography, and carotid IMT was assessed by ultrasound measurements and compared with age‐specific reference values. Results: The median CACS in all patients was 35 (IQR 0–110) and the geometric mean IMT was 0.80 mm (95% confidence interval [CI] 0.76–0.84); neither was different from the reference values. Patients with a previous MACE (n = 9) had significantly higher CACS and IMT than patients without a previous MACE: CACS median 1013 (IQR 530–1306) vs. 0 (IQR 0–67), and IMT geometric mean 1.09 mm (95% CI 0.95–1.26) vs. 0.76 mm (95% CI 0.73–0.79), both P < 0.001. A higher calculated 10‐year cardiovascular risk was related to higher IMT and CACS. Conclusion: Patients with hemophilia are not protected against the development of atherosclerosis as measured by CACS and IMT. The extent of atherosclerosis is related to the traditional cardiovascular risk factors. This suggests that traditional cardiovascular risk factors should be monitored and treated in patients with hemophilia.     

Hemostatic cardiovascular risk factors,common carotid–intima medial thickness and peripheral arterial disease in South Asians and African Caribbeans: a substudy to the Ethnic‐Echocardiographic Heart of England Screening (E‐ECHOES) Study

Summary. Objective: To determine whether ethnic differences exist in inflammatory (interleukin‐6 and C‐reactive protein) and hemostatic biomarkers (soluble P‐selectin [sP‐sel], von Willebrand factor [VWF], and fibrin D‐dimer) between South Asian (people originating from India, Pakistan, and Bangladesh) and African Caribbean (Black Caribbean and Black African) groups, the two largest minority ethnic groups in the UK; and to determine associations between these biomarkers and common carotid intima–media thickness and peripheral artery disease (PAD). Patients and methods: We recruited 572 subjects (356 South Asian and 216 Black) aged ≥ 45 years as a substudy to a community screening project, the Ethnic‐Echocardiographic Heart of England Screening (E‐ECHOES) study. All subjects completed an interviewer‐led questionnaire, anthropometric measurements were taken, and blood sampling was performed if consent was granted. Ankle brachial pressure index (ABPI) was calculated, and the common carotid intima–media thickness (CCIMT) was measured. PAD was defined as ABPI < 0.9. ELISA was used to quantify inflammatory and hemostatic biomarkers. Results: The incidence of hypertension (> 70%) and diabetes (> 27%) was high, but non‐significantly different between the two ethnic groups. South Asians had higher platelet count and sP‐sel levels than African Caribbeans (P < 0.0001 for both), despite there being no significant difference in antiplatelet medication. African Caribbeans had higher D‐dimer levels (P = 0.0052). Among South Asians, VWF correlated with ABPI (P = 0.047) and mean (P = 0.002) and maximum CCIMT (P = 0.011) on univariate analysis, and remained an independent predictor of mean and maximum CCIMT on multivariate analysis with traditional cardiovascular risk factors (P = 0.034 and P = 0.046, respectively). In African Caribbeans, D‐dimer levels were was higher in PAD than in normal ABPI participants (P = 0.04), and was associated with ABPI in both univariate analysis (P = 0.014) and multivariate analysis (P < 0.0001) with traditional cardiovascular risk factors. Conclusion: Ethnic differences are evident in inflammatory and hemostatic factors, as well as in their associations with CCIMT and PAD. These may reflect differences in cardiovascular risk factors or pathophysiologic processes that characterize each ethnic group.     

高频超声在腹外疝类型鉴别中的应用

目的探讨高频超声在腹外疝类型鉴别中的价值;方法用高频超声探测站立住至仰卧位时腹股沟肿块情况,了解肿块的形态、走行情况以及与腹股沟管或腹股沟韧带的关系、体位改变时的变化及腹壁下动脉的位置结果高频超声诊断腹外疝69例;均经手术证实,其中52例为斜疝,15例直疝,2例股疝结论高频超声能明确鉴别斜疝、直疝、股疝,可作为腹外疝外科手术前的首选鉴别方法。     

缬沙坦对高血压患者左心室壁厚度和舒张功能的影响

目的观察缬沙坦的降压效果,及其对左心室壁厚度和舒张功能的影响。方法对55例高血压患者使用缬沙坦降压治疗6个月,观察其降压效果及对左心室功能影响。结果治疗6个月后患者血压明显下降,收缩压平均下降27.7 mm Hg(1 mm Hg=0.133 kPa),舒张压平均下降16.4 mm Hg,左心室壁厚度及左心室舒张末期内径也明显下降。结论缬沙坦降压效果较好,且不良反应轻微,并可逆转左心室肥厚及改善左心室舒张功能。     

Short-term therapy with relatively low-dose cerivastatin improves endothelial function independently of its lipid-lowering effect: Evaluation of brachial artery vasodilatation using B-mode ultrasound imaging

Background and Objective Administration of 0.4 to 0.8 mg of cerivastatin per day for 2 weeks has been reported to have pleiotropic effects and improve endothelial function. Whether low-dose cerivastatin would produce these rapid pleiotropic effects in the clinical setting remains uncertain, however. We investigated the effect of short-term therapy with relatively low-dose cerivastatin (0.15 mg/day) on endothelial function, thrombostatic parameters, and C-reactive protein (CRP) levels in hypercholesterolemic patients. Methods Thirteen patients with LDL-cholesterol>160 mg/dl were treated with daily doses of 0.15 mg of cerivastatin for 2 weeks. Endothelial function, thrombostatic parameters (tissue-type plasminogen activator [t-PA], plasminogen activator inhibitor type 1 [PAI-1], and CRP were estimated at baseline and again after 2 weeks of treatment. Endothelial function was measured as flow-mediated vasodilation. Flow-mediated vasodilatation was assessed by measuring the percent change in the diameter of the brachial artery in response to reactive hyperemia using high-resolution ultrasound. Endothelium-independent vasodilatation was also measured using sublingual nitroglycerin. Results No major complications developed after the treatment. Total cholesterol decreased significantly, from 258±32 to 211±21 mg/dl, and LDL-cholesterol also decreased from 171±15 to 133±16 mg/dl after the treatment. Flow-mediated vasodilatation increased significantly, from 4.6±1.3 percent to 8.7±3.5 percent after 2 weeks of therapy, although endothelium-independent vasodilatation was not affected (9.5±2.4% vs 8.8±3.1%). No relation was found between percent change in flow-mediated vasodilatation and improvement in levels of LDL-cholesterol after therapy (r=0.07). PAI-1, t-PA, and CRP were not significantly changed by 2 weeks of therapy. Conclusions (1) Evaluating vasodilation of the brachial artery with B-mode ultrasound imaging was useful in investigating the effect of statin on endothelial function. (2) Although no effect was detected in PAI-1, t-PA, or CRP, relatively low-dose cerivastatin therapy for 2 weeks improved endothelial function and lipid level independently and safely in hypercholesterolemic patients.     

靶向超声介导血管内皮生长因子基因转染对兔损伤动脉血管内皮功能的影响

目的研究超声造影剂SonoVue携带血管内皮生长因子(VEGF)基因靶向转染兔损伤动脉后血管内皮功能的恢复及程度。方法构建真核表达质粒pCDNA3.1(-)/hVEGF165。建立兔髂外动脉的球囊损伤模型,并随机分为两组:损伤后血管腔内注射携带VEGF基因质粒的造影剂并接受超声辐照的为实验组,损伤后无任何干预为对照组。2周后超声检测髂外动脉内皮依赖性舒张功能,完成后将兔处死取损伤处血管,HE染色计算血管内膜与中膜面积比值,免疫组化了解血管壁平滑肌细胞的增殖和VEGF的表达情况。结果实验组髂外动脉血管内皮依赖性舒张功能较对照组改善(P<0.05),但实验组的血管内膜面积与中膜面积比值与对照组比较,差异无统计学意义(P>0.05)。免疫组化显示实验组血管壁平滑肌细胞增殖核抗原表达明显减低,且见大量VEGF阳性反应的棕褐色颗粒。结论靶向超声介导VEGF基因转染损伤的动脉管壁2周即可有效改善局部血管的内皮功能,有效增强VEGF的表达,并且抑制平滑肌细胞增殖,提示携基因靶向超声可以为早期改善介入治疗后血管内皮功能并由此防治再狭窄提供新途径。     

Improved imaging of the carotid artery in the short-axis plane by a mechanical scanning ultrasonic probe

To image the intima–media complex of the carotid artery in a wider region, a method for measuring cross-sectional images in the arterial short-axis plane is presented. Using the proposed mechanical scanning system for an ultrasonic probe, cross-sectional images of a silicon rubber tube and a human carotid artery are measured in basic experiments and in in vivo experiments, respectively. These experiments show that this method successfully images the short-axis cross sections. Using the method proposed in this article, B-mode images in the short-axis plane can be accurately measured in a wider region than is possible with conventional methods.     

The effect of cholesterol lowering on carotid and femoral artery wall stiffness and thickness in patients with familial hypercholesterolaemia

BACKGROUND: Early in the process of atherosclerosis, changes in vessel wall stiffness and thickness may occur. The present study evaluates the effect of cholesterol reduction on artery wall stiffness and intima media thickness in patients with familial hypercholesterolaemia (FH). MATERIALS AND METHODS: Forty-five patients with familial hypercholesterolaemia (mean age 46+/-10 years) with untreated LDL cholesterol concentration > 9 mmol L(-1), were studied before and after one year of cholesterol lowering therapy with statins (simvastatin, atorvastatin 40-80 mg day(-1). The distensibility (DC in 10-3 kPa(-1) and compliance (CC in mm2. kPa(-1) of the common carotid artery (CCA) (right and left side) and common femoral artery (CFA) (right side) were determined by a wall track system (Pie Medical). The intima media thickness (IMT) (both right and left) of the CCA, bulb (BUL), internal carotid artery (ICA) and CFA were measured in mm by high-resolution ultrasound (Biosound). RESULTS: The mean concentration of total cholesterol (TC), LDL-cholesterol (LDL-C) and triglycerides (TG) were reduced significantly by 43%, 51% and 25%, respectively, whereas HDL-cholesterol (HDL-C) increased by 13% (P<0.001). In the CFA, the DC and CC increased significantly (DC from 7.9+/-3.0 to 9.1+/-3.7 in 10(-3) kPa(-1); CC 0.5+/-0.2-0.6+/-0.3 in mm2. kPa(-1), whereas the DC and CC did not change in the CCA. In contrast, the IMT of the CCA decreased significantly in both men and women whereas an IMT decrease was also seen in the BUL and ICA in premenopausal women. A LDL-cholesterol reduction of 44.8% and 45.4% was necessary to induce significant decreases in IMT and increases in DC and CC. CONCLUSIONS: One year of cholesterol lowering therapy in FH decreases the wall stiffness in the CFA and the arterial wall thickness in the CCA.     

超声射频信号技术分析妊娠高血压综合征孕妇颈动脉血管功能的研究

目的采用超声射频信号血管分析技术对妊娠高血压综合征(PIH)孕妇颈动脉内中膜厚度及弹性进行综合评估,并与正常妊娠孕妇比较,观察PIH孕妇颈动脉血管功能的变化.方法PIH孕妇27例(PIH组),平均动脉压108 mm Hg(1 mm Hg=0.133 kPa),采用年龄及孕周匹配的30名正常妊娠孕妇作为健康对照组.彩色多普勒超声诊断仪分别启用超声射频信号技术中的血管内-中膜定量技术(QIMT)及血管硬度定量分析技术(QAS)测量两组孕妇颈动脉内-中膜厚度IMT及弹性.结果 PIH组孕妇颈总动脉IMT、脉搏波传播速度(PWV)、等容收缩期到射血期转折点压力(PT1)、动脉增强压(AP)及动脉压增强指数(AIx)分别为(466.84±118.50)μm、(7.09±1.97)m/s、(127.50±14.29)mm Hg、(5.14±3.39) mm Hg及(7.58±8.73)%,健康对照组分别为(386.58±125.79)μm、(5.95±1.11) m/s、(105.89±11.02)mm Hg、(1.98±2.19)mm Hg及(-4.79±7.92)%.两组比较差异有统计学意义(t值分别为2.660、2.660、3.460、3.460、3.460,P值均＜0.01).结论 与正常妊娠孕妇比较,PIH孕妇颈动脉内中膜明显增厚,弹性减低.超声射频信号血管分析技术可敏感地反映弹性血管结构和功能变化.