European Journal of Vascular & Endovascular Surgery
Volume 33, Issue 2 , Pages 149-153, February 2007

Carotid Intima-media Thickness in Patients with Abdominal Aortic Aneurysms

Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong, China

Accepted 4 September 2006. published online 13 November 2006.

Article Outline

Objective

The contribution of atherosclerosis to the development of Abdominal Aortic Aneurysms (AAA) is still controversial. Ultrasound scans can detect intima-media thickening of the carotid arteries as an early sign of atherosclerosis. The aim of this study was to investigate whether patients with Abdominal Aortic Aneurysms (AAAs) have thickened carotid IMT as patients with atherosclerotic peripheral arterial disease (PAD).

Methods

With high-resolution B-mode ultrasonography, the intima-media thickness (IMT) in the carotid arteries (right and left common carotid artery) was measured in AAA patients and compared with that of age and sex-matched patients with atherosclerotic peripheral arterial disease (PAD). A third group of healthy age and sex- matched control subjects were included for comparison. The corresponding carotid artery lumen was also determined in all groups. Comparison of the three groups was made by ANOVA.

Results

Fifty-eight AAA patients and 69% were men (mean age of 72.3 years) were studied. Aged and sex-matched groups comprised of 111 PAD patients and 71 healthy. The mean carotid IMT was highest in PAD patients (1.036±0.18mm). The values of controls and AAA patients were similar and significantly lower than that of atherosclerotic patients (0.875±0.11mm and 0.812±0.53mm respectively, both p<0.005 vs. PAD). Narrowing of the corresponding lumen was found in PAD patients compared with that of AAA patients, but no difference can be seen between healthy subjects and AAA patients. The mean carotid IMT was greater in men (P<0.05) in all studied groups, but no similar gender specificity was found in the lumen diameter.

Conclusions

This study shows that the carotid artery IMT of AAA patients is similar to healthy subjects, but not as thick as patients with atherosclerotic disease. As carotid (IMT) is a surrogate marker of atherosclerosis, the findings support the notion that the formation of AAA may not be fully atherosclerosis-dependent. Gender may be a confounding factor for carotid intima-media thickening.

Keywords: Carotid, IMT, Abdominal aortic aneurysm

 

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Introduction 

Peripheral arterial disease (PAD) and abdominal aortic aneurysm (AAA) present a common vascular condition with morbidity and life-threatening implications in the elderly. Previously, both diseases were thought to be totally atherosclerosis-dependent, having similar atherosclerotic risk factors with regard to smoking habit, age, hypertension, ischemic heart disease and lipid levels.1 However, the common cause of AAA is atherosclerosis has been challenged by cumulative studies.2, 3, 4 There is also evidence that the two diseases affect distinct layers of the arterial wall; atherosclerosis mainly involves the inner layers, intima, and media, whereas AAA typically affects the outer layers, media and adventitia.5 The dilatative manifestation of AAA is also the opposite of the occlusion characteristic of atherosclerotic diseases. The reasons for the occurrence of these two differing conditions remain obscure.

Noninvasive B-mode ultrasound evaluation of carotid intima-media thickness (IMT) is proved to be helpful in evaluating atherosclerosis which in turn contributes to the different manifestations of arterial diseases.6, 7, 8, 9 Measurement of carotid artery is also easily assessable, particularly in patients with high body mass index10 and is independent of the blood pressure.8 Several population studies have shown that carotid IMT is significantly higher in patients with atherosclerotic peripheral arterial disease (PAD).7, 8, 9 Previous ultrasonographic study on a small group of AAA patients suggested that AAA patients with atherosclerotic diseases had thicker carotid IMT than with AAA alone.11 However, still relatively little attention has been paid to the carotid arterial characteristics of AAA patients. IMT is proven to be an indicator of generalized atherosclerosis.12, 13, 14 Our study attempts to investigate the extent of which atherosclerosis contributes to the formation of AAA by determining the carotid IMT, which is located remotely from the aneursymal aorta, in AAA patients and compare it with that in PAD patients and healthy subjects.

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Material and Methods 

Patients 

Fifty-eight consecutive patients who have AAA were examined by carotid ultrasound from January 2003 to September 2005. The mean aneurysm size was 6.07+2.5cm (4.5–10cm) diameter.

Symptomatic PAD participants (n=111) were identified in our clinic. They were selected to be age- and sex-matched with the AAA patients. The diagnosis of PAD was made by means of clinical evaluation, ankle branchial index measurements (ABI), treadmill exercise test and duplex ultrasonography.

Healthy Chinese subjects (n=71) with ankle brachial index of 1 or higher and with no manifestation of atherosclerosis were recruited as controls in the study. They were recruited from local health check programs and others were varicose vein patients at the same local hospital and again selected to match the overall age and sex distribution of AAA patients. Exclusion criteria for control group were hypertension, hyperlipidemia, diabetes mellitus and history of cardiovascular or cerebrovascular disease.

Previous investigations have shown that an increased IMT is commonly associated with the presence of stenotic lesions in the carotid arteries.15 AAA and PAD patients who have concomitant carotid stenosis measured with color Doppler-assisted duplex scanning were excluded from the study.

All patients were examined by one experienced registered vascular technologist in our vascular laboratory. The IMT of the left and right common carotid artery were visualized in all subjects.

Measurement of Intima-media thickness (IMT) 

For measuring Intima-media thickness (IMT) of the right and left common carotid arteries and lumen diameter (LD), a longitudinal view of the common and internal carotid artery was obtained by colour flow Doppler US scanning system (Acuson 128XP-10 system, 5MHz probe; Acuson, Mountain View, Calif). The image was recorded on videotape, and then measured manually by tracing a cursor along the echo edges on a 10mm section with the aid of the digitizer.16 The 10mm longitudinal image provides approximately 100 boundary points between the echo edges where the IMT was measured, and the mean value of IMT was automatically calculated with a computerized system. IMT was measured on the far wall, from the interface between blood and intima and the interface between media and adventitia.16 The intimal-medial thickness (IMT) was determined by the measurements taken at the common carotid artery away from the atherosclerotic plaque and averaged over three readings on two good quality images.

Statistical analysis 

The IMT of common and internal carotid artery lumen values were normally distributed. Comparisons were made among the AAA, control and PAD groups. IMT and LD were measured in mm. All data were expressed as mean±standard deviation (S.D.) and pairwised comparison was made by analyses of covariance (ANCOVA) using SPSS version 13.0 for Windows (SPSS Inc, Chicago, IL, U.S.A). A p value of less than 0.05 was considered to be statistically significant.

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Results 

The diseased groups were all matched for age and sex. The average age of the AAA patients and PAD patients were 72.3±8.73 (45–80) years and 71.5±9.48 (52–80) years respectively with a male to female ratio of 2.2:1. The control group was 65+11.32 (40–78) consisted of 48 healthy male and 23 healthy female participants. The ultrasonography findings are summarized in the Table 1. The mean carotid IMT of AAA patients (0.875±0.11mm) was similar to that of the age and sex-matched control group (0.812±0.53., no statistical difference). AAA also had similar lumen diameter (6.05±0.71mm) with control groups (6.01±0.75mm). The mean carotid IMT of PAD patients (1.036±0.18mm) was the highest and significantly greater than that of the AAA patients (p=0.005). The common carotid artery lumen was narrower for the PAD patients (5.8±0.82mm) compared with the AAA patients (6.05±0.71mm, p=0.033).

Table 1. Intima-medial thickness (IMT) and lumen of carotid artery in patients with PAD, AAA and control subjects
Mean±S.D.p-value
Group I: PADGroup II: AAAGroup C: ControlGroup:
I-III-CII-C
IMT (mm)1.036±0.180.875±0.110.812±0.530.005<0.0010.322
LD (mm)5.8±0.826.05±0.716.01±0.750.0330.010.840

The mean carotid artery IMT and lumen diameter of female and male patients in the three groups is shown in Table 2. Mean carotid IMT was greater in men than in women in all studied groups (P<0.05). Lumen diameter of the common carotid artery showed no association with gender.

Table 2. Differences in the intima-medial thickness (IMT) and lumen of carotid artery between male and female patients of the three groups
IMT (mm)LD (mm)
MaleFemaleMaleFemale
Group I: PAD1.05±0.16∗0.96±0.155.5±0.925.9±0.65
Group II: AAA0.89±0.14⇕0.79±0.096.0±0.956.06±0.55
Group C: Control0.87±0.11∗0.76±0.106.1+0.255.9+0.98

∗p<0.05 vs. female patients.

⇕p<0.02 vs. female patients.

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Discussion 

Research into the pathophysiology of abdominal aortic aneurysm (AAA) is difficult because the cause of the disease is multifactorial. Although patients with abdominal aortic aneurysms (AAA) frequently have coexisting systemic atherosclerosis, the dilatative manifestation of AAA is the opposite of the occlusion characteristic of atherosclerotic diseases. Cumulative data have suggested that this dilatative disease is caused by an alteration in connective tissue metabolism in systemic arterial wall rather than initiated by atherosclerosis. A highly specific cDNA microarray study found that five genes had differential expression between AAA and atherosclerotic peripheral arterial disease (PAD).17 Risk factors in aneurysm patients have also been found to be different from that in patients with PAD. For example, diabetes mellitus is not as common in AAA as in PAD.18 In addition, non-cardiovascular factors such as inguinal herniation and chronic obstructive pulmonary disease, have been ascertained with AAA, but not with PAD, suggesting that connective tissue disorders are associated in the development of AAA.19 This phenomenon raised the question of whether two disease processes are caused or initiated by different factors.

IMT, the combined thickness of the intima and media measured on duplex scan, is a good reflection of the intima medial thickness on histological examination16, 20, 21 and is an accurate technique to determine the IMT in superficial arteries. Its reproducibility and validity as a measure of the atherosclerosis process and as a marker of cardiovascular diseases have been well established in cardiovascular disease patients. The results of the current study demonstrated that the mean common carotid IMT in patients with AAA was similar to that of the control group and significantly lower than in PAD patients. These results were consistent with the Second Manifestations of ARTerial disease (SMART) study in Netherlands. Their AAA patients had slightly higher carotid IMT than ours, but on average were not thick as that of PAD patients.8 Those results implied that aortic aneurymal disease is not associated with a high prevalence of systemic atherosclerosis. Assuming that the development of PAD is fully determined by atherosclerosis, those findings suggested that atherosclerosis only contributes partly to the development of AAA.

In our studied groups, it was not surprising that gender difference in IMT was found in all our patients. Some studies suggested that hormonal factors might reduce arterial wall stiffness and intima-media thickening.22, 23 The gender difference in IMT is also in agreement with most studies of superficial arteries with the notion that the male sex seems to be a risk factor for intima-media thickening.24, 25

It is well known that thickening of the intima is associated with aging.23 Mean IMT values in our PAD group were age-matched with all AAA patients suggesting that the aging process does not contribute significantly to the elevated IMT values in atherosclerotic disease group.

Nevertheless, some limitations of IMT measurement study existed. Mainly, there is no uniformity in the definition of carotid IMT. The EAS measured the carotid artery 2cm proximal to the bifurcation from both sides and carotid IMT was defined as the maximum of these two readings.7 The Rotterdam study13 used the average value from the two common carotid arteries, each with three readings obtained from the 1cm distal to the bifurcation. Another European study took multiple readings of the thickness every 100μm along a 1cm longitudinal length of the artery 2 to 3cm proximal to the bifurcation. The carotid IMT was also defined as the average of the left and right sides.26 The Atherosclerosis Risk in Communities (ARIC) study27 used the average of the readings taken from the common carotid artery, the carotid bifurcation and internal carotid artery of both sides. Measurement of the maximum carotid IMT and the mean IMT over a length of 1cm is similar but the latter had a better reproducibility in an observation study.6 The extent of thickened IMT found in our diseased groups as compared with control groups was consistent with values reported in England. Their ARIC study involved the measurement of mean carotid IMT in white men with peripheral arterial disease was 0.16mm thicker than in disease-free participants.7 The CCA is also strongly recommended to be included in the studies of atherosclerosis.28 Therefore, our study of measuring the mean IMT of common carotid artery should be reliable and reproducible. Though the adventitial layer was excluded in our study, the major part of total wall thickness is included in IMT measurements.29 Our results further indicated that IMT of carotid artery can be regarded as a surrogate marker of atherosclerosis in arterial disease patients as suggested by other population studies.7, 8, 9

In conclusion, the mean common carotid IMT in AAA patients was similar to healthy subjects and significantly lower than PAD patients. The findings support the notion that the formation of AAA is not fully atherosclerosis-dependent. In addition, gender differences in IMT found in the common carotid artery of men might be an important indicator of aneurysm development. Treatment of some cardivovascular risk factors is associated with a diminished progression of the IMT, paralleled by an improvement in the symptoms associated with atherosclerotic diseases.10 Further studies to explore the possibility of diminishing the thickening of IMT in male aneurysmal patients are awaited.

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PII: S1078-5884(06)00506-5

doi:10.1016/j.ejvs.2006.09.008

European Journal of Vascular & Endovascular Surgery
Volume 33, Issue 2 , Pages 149-153, February 2007

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