Asymptomatic Occlusive Lesions of Carotid and Intracranial Arteries in Japanese Patients With Ischemic Heart Disease
Evaluation by Brain Magnetic Resonance Angiography
Background and Purpose The purpose of this study was to elucidate the prevalence and degree of asymptomatic occlusive lesions in the carotid and intracranial arteries in Japanese patients with ischemic heart disease (IHD).
Methods We performed carotid and intracranial MR angiography (MRA) on 67 patients (49 men, 18 women; age range, 40 to 78 years; mean age, 60.1 years) who had received selective coronary angiography for the clinical diagnosis of IHD. On the basis of these images, degree of stenosis in the regions of the bilateral carotid artery bifurcation and five regions of the intracranial arteries, ie, bilateral intracranial portions of the internal carotid arteries and the middle cerebral arteries and the basilar artery were estimated.
Results Stenosis of more than 25% narrowing of the diameter of the target arteries was found in 15 patients (22.4%) in the extracranial carotid arteries and in 11 patients (16.4%) in the intracranial arteries. Most of the stenotic lesions were mild. The incidence of extracranial carotid stenosis and the severity of coronary atherosclerosis showed a significant correlation. The mean age of the patients with intracranial arterial lesions was statistically higher than those without intracranial lesions.
Conclusions Our data suggest that asymptomatic occlusive lesions in the carotid and intracranial arteries are fairly common in Japanese patients with IHD, although the degree of stenosis is relatively mild. Coexistence of carotid atherosclerosis should be suspected in IHD patients with severe coronary atherosclerosis, and the possibility of atherosclerosis in the intracranial arteries should be considered in aged IHD patients.
Atherosclerosis is a systemic and progressive disease process. It has been demonstrated that patients with IHD are more likely to suffer from stroke,1 while patients with ischemic stroke die more frequently from myocardial infarction than from recurrent stroke or other neurological disease.2 3
Previous studies have shown a racial difference in prevalent sites of atherosclerotic lesions.4 5 6 7 8 In whites the extracranial carotid arteries are more affected than the intracranial arteries, while in Asians and blacks the intracranial arteries are more affected. It is also known that in white populations a correlation between the extent of coronary atherosclerosis and extracranial carotid atherosclerosis is strong.4 8 9 10 11 12 13
In Japan, a recent change of lifestyle is believed to have caused an increase of the incidence of extracranial carotid artery disease and IHD.6 7 However, studies investigating the relationship between cerebral and coronary atherosclerosis in Japanese patients are scarce.
We therefore performed carotid and intracranial MRA on patients with IHD to explore the prevalence and extent of asymptomatic cerebral artery occlusive lesions complicating IHD in Japanese patients.
Subjects and Methods
Among patients who received selective coronary angiographic examinations in our hospital between October 1993 and February 1994 for the clinical diagnosis of myocardial infarction or angina pectoris, 67 subjects who agreed to undertake the examination and signed an informed consent were studied prospectively. All subjects underwent MRA studies of extracranial carotid and intracranial cerebral arteries within 3 months of the coronary angiography. They included 49 men and 18 women ranging in age from 40 to 78 years, with a mean of 60.1 years. Forty-five patients had a myocardial infarction and 22 had angina pectoris. None had a history of stroke.
All MRA examinations were performed with a 1.0-T MR system (Magnetom Impact; Siemens). Images were acquired by a three-dimensional, Fourier transform time-of-flight method with a spoiled gradient-echo sequence. For extracranial carotid MRAs, the repetition time was set for 40 milliseconds, echo time for 10 milliseconds, and a flip angle for 20°. The number of excitations per phase encoding was 1. A 128×128×64 matrix was used, with a field of view of 180×180 mm and a partition thickness of 1.6 mm, resulting in a 1.4×1.4×1.6 voxel. We chose this relatively small matrix and field of view to maintain high resolution without increasing the examination time. The axial images thus acquired and magnified to 256×256 with interpolation were used as source data for the construction of projection images with use of a maximum-intensity-pixel projection algorithm. In each case, 10 projection images at 18° increments horizontal over a 180° range were obtained.
The parameters of intracranial MRA were repetition time of 35 to 40 milliseconds, echo time of 7 milliseconds, and a flip angle of 15°. The number of excitations was 1. We used two volume slab orientations, a horizontal section and a section parallel to the clivus, thereby covering the view and compensating the signal attenuation due to flow direction. A 128×128×64 matrix was used, with field of view of 120×120 mm and a partition thickness of 1 mm, resulting in a 0.94×0.94×1-mm voxel. The axial images thus acquired were used as source data for the construction of projection images with use of a maximum-intensity-pixel projection algorithm. In each case, nine projection images at 22.5° increments vertical and horizontal over a 180° range were provided.
Two neurologists (T.U., M.T.), who were blinded to all clinical information, independently reviewed the MRAs. Degree of stenosis was divided into five grades depending on the narrowness of the arteries, ie, normal, mild, moderate, severe, and occluded. Less than 25% reduction of an arterial diameter was graded normal, 25% to 49% reduction mild, 50% to 74% reduction moderate, 75% to 99% reduction severe, and no opening was graded occluded.14 15 The state of the extracranial portion of the ICA was evaluated at the bifurcation site by the carotid MRA, and that of the intracranial arteries at the intracranial portion of the ICA, at the horizontal portion of the MCA, and at the BA by the intracranial MRA. To measure the percent stenosis of extracranial portion of the ICA, we compared the diameter of maximal stenosis with that of the normal-appearing proximal ICA beyond the carotid bulb.16
The severity of coronary artery atherosclerosis was evaluated by CAS, which was defined as the number of affected coronary branches, ie, the right and left anterior descending branches and left circumflexus with more than 75% narrowing of the diameter.17 18
For risk factor evaluation, we investigated the presence or absence of hypertension, diabetes mellitus, hyperlipidemia, and habit of smoking. Hypertension was judged present when systolic pressure was consistently above 160 mm Hg or diastolic pressure consistently above 95 mm Hg or when the patient had a history of treatment for hypertension. Diabetes mellitus was diagnosed when a fasting blood glucose level was above 140 mg/dL or when the patient had a history of treatment for diabetes mellitus. Hyperlipidemia was defined when a serum total cholesterol level was above 220 mg/dL, triglyceride level was above 150 mg/dL, high-density lipoprotein cholesterol level was below 40 mg/dL, or when the patient had a history of treatment.
We used Fisher’s exact test for analysis of discrete variables and Student’s t test or the Mann-Whitney U test for analysis of continuous variables.
The status of extracranial and intracranial arteries of the 67 subjects is summarized in Table 1⇓. Each number indicates the sum of the involved vessels. Extracranial carotid stenosis was found in 15 patients (22.4%). Eleven patients had mild stenosis, 3 moderate, and 1 severe. Intracranial arterial stenosis was found in 11 patients (16.4%). Eight patients had mild stenosis, 1 moderate, and 2 severe. Four patients had both carotid and intracranial lesions. Thus, 22 patients (32.8%) showed MRA changes related to the cranial arteries.
Fig 1⇓ shows the prevalence of arterial changes in terms of the age group. The number of patients showing stenosis tended to increase for both extracranial carotid and intracranial arteries with advancing age. The tendency is clearer for intracranial arterial lesions.
Table 2⇓ summarizes the incidence of the risk factors in terms of CAS score. Among these 67 patients with IHD, 60 had at least one coronary artery with 75% or more stenosis. Of these 60 patients, 1 coronary artery was involved in 31 patients, 2 arteries in 22, and 3 in 7 patients. All 7 patients with a CAS score of 0 had no significant coronary artery stenosis. The mean age of the CAS 0 group was significantly younger than that in the other groups. No significant correlation was found between the incidence of four risk factors and the number of involved coronary arteries.
The relationship between the percentage of the number of patients with affected cerebral arteries and the CAS score is presented in Fig 2⇓. The number of the patients showing extracranial carotid artery lesions increased as the CAS scores increased. The prevalence of extracranial carotid stenosis in the CAS 3 group was significantly greater compared with the CAS 0 and 1 groups (P<.05). Moderate to severe stenosis was found only in the CAS 2 and 3 groups. The prevalence of intracranial arterial stenosis was not correlated with the severity of coronary stenosis.
The clinical characteristics of the patients with and without cerebral artery lesions are compared in Table 3⇓. The mean CAS of the patients with carotid lesions was significantly higher than that of the patients without such lesions (P=.011). The incidence of diabetes mellitus was significantly higher in the patient group with carotid lesions than in the group without such lesions (P<.05). The mean age of the patients with intracranial artery stenosis was statistically higher than that of the patients without stenosis (P=.003). Incidence of hypertension was significantly higher in the patient group with intracranial arterial lesions than in the group without such lesions (P<.05).
Our previous study on the relationship between coronary and cerebral arterial atherosclerosis in Japanese patients with a history of both ischemic stroke and IHD who underwent cerebral and coronary angiographies showed a significant correlation between the severity of atherosclerosis of the extracranial carotid arteries and that of the coronary arteries.19 However, the severity of atherosclerosis of the intracranial arteries was unrelated to that of the coronary arteries. The data were consistent with those reported for white populations, but we still do not know whether these results are true for IHD patients who do not have ischemic cerebral events. The present prospective study was aimed at elucidating the prevalence and degree of asymptomatic occlusive lesions in the cerebral arteries in Japanese IHD patients.
We used MRA as a neuroimaging technique because it is noninvasive and can detect occlusive changes not only in the extracranial but also in the intracranial arteries.14 15 20 21 We have already confirmed the high sensitivity (>95%) and specificity (>85%) of the three-dimensional time-of-flight MRA method for evaluating the status of cranial arteries.14 15 Among 67 IHD subjects, asymptomatic extracranial carotid stenosis of more than 25% narrowing was detected in 15 patients (22.4%) and asymptomatic intracranial arterial stenosis in 11 patients (16.4%). Although the degree of stenosis was relatively mild, it should be considered that asymptomatic occlusive lesions in the cerebral arteries are not uncommon in the population of Japanese IHD patients. The higher prevalence of extracranial carotid lesions compared with intracranial arterial lesions is consistent with the data reported on white populations.
There have been a few studies concerning the frequency and degree of asymptomatic extracranial carotid lesions in IHD patients. Sanguigni et al22 found a reduction in diameter of more than 50% on echo-Doppler ultrasonography in 27.7% of 187 coronary arterial disease patients. Approximately 59% of these patients were completely asymptomatic. Andersen et al23 noted that only 8% of the patients with coronary arterial disease showed hemodynamically significant carotid arterial disease on oculopneumoplethysmography. Barnes et al,24 in their prospective screening of asymptomatic carotid disease in patients undergoing cardiovascular surgery, reported that the prevalence of asymptomatic carotid obstructive lesions, defined as more than 50% diameter reduction by the Doppler ultrasound method, was 12.3% of 324 patients with coronary artery disease.
Tanaka et al25 performed an ultrasonographic study of 92 IHD patients who had received selective coronary angiography and detected silent carotid atheromatous plaques in 50.9% of the group that showed significant stenosis of more than 75% in the coronary arteries and in 34.3% of the group that showed no significant coronary arterial change, demonstrating a correlation between the silent extracranial carotid atheromatous lesion and the severity of coronary atherosclerosis. Unfortunately, details of the carotid stenosis were not described. In the present study we were able to demonstrate that the prevalence of asymptomatic carotid lesions was related to the severity of coronary atherosclerosis.
Although a few autopsy studies confirmed a correlation between intracranial and coronary atherosclerosis,26 27 28 clinical studies on this important issue remained obscure partly because of limited resources in terms of diagnostic tools. Our previous study showed a lack of correlation between these two pathologies.19 To our knowledge there have been no clinical studies of the prevalence and severity of asymptomatic intracranial occlusive lesions in IHD patients. In the present study approximately 16% of the IHD patients were shown to have coexistent intracranial occlusive arterial changes that were asymptomatic and comparatively mild in degree. The prevalence of the intracranial arterial lesions was correlated with age but not with the severity of coronary artery stenosis.
Coronary and cerebral atherosclerosis have been demonstrated to have many common risk factors, ie, age, hypertension, diabetes mellitus, hyperlipidemia, and smoking, but the relative impact of the individual risk factors differs between the two.29 Of all known risk factors, age has the strongest association with atherosclerotic lesions regardless of the site of arteries.10 30 In the present study the prevalence of both extracranial carotid and intracranial arterial lesions tended to increase with advancing age. The mean age of the patients with intracranial lesions was significantly higher than that of the patients without intracranial lesions (P=.003), while the mean age of the patients with extracranial carotid lesions was not significantly different from that of the patients without such lesions.
The fact that only four patients had occlusive lesions in both the extracranial carotid and intracranial arteries may suggest that risk factors related to two arterial territories are different. Among hypertension, diabetes mellitus, hyperlipidemia, and smoking, the incidence of diabetes mellitus was significantly higher in the IHD patients with extracranial carotid lesions than in those without such lesions (P<.05). Handa et al30 found that diabetes mellitus was a possible risk factor for extracranial carotid atherosclerosis in the Japanese. Crouse et al10 reported that diabetes mellitus was a significant risk factor for carotid atherosclerosis when their data were assessed by univariate analysis but was not significant when assessed by multivariate analysis. The prevalence of hypertension in our IHD patients with intracranial arterial lesions was significantly higher than in those without such lesions (P<.05). This association between hypertension and occlusive lesions of the intracranial arteries has been reported.8 31
We conclude that there is a trend that asymptomatic occlusive lesions in the cerebral arterial territories, although mild in degree, are increasing, at least in the Japanese population of patients suffering from IHD. Coexistence of carotid atherosclerosis should be suspected in IHD patients with severe coronary atherosclerosis, and the possibility of atherosclerosis in the intracranial arteries should be considered in aged IHD patients.
Selected Abbreviations and Acronyms
|CAS||=||coronary angiography score|
|ICA||=||internal carotid artery|
|IHD||=||ischemic heart disease|
|MCA||=||middle cerebral artery|
|MRA||=||magnetic resonance angiography|
- Received July 24, 1995.
- Revision received November 29, 1995.
- Accepted November 29, 1995.
- Copyright © 1996 by American Heart Association
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