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Evaluation of thoracic aortic atherosclerosis by transesophageal echocardiography
Volume 127, Number 2 American Heart Journal
degeneration and vessel stiffness and introduced the term atherosclerosis to indicate this combination.2 Blankenhorn and Kramsch3 reported that further studies of atherosclerosis should use a combination of measures to evaluate both atherosis and sclerosis. Atherosis represents the grade of atheroma morphologically, and sclerosis represents functional changes in arterial stiffness. In this study we measured the thickness of the intima-media complex4T 5 as an index of atherosis and determined the stiffness parameter @I 7 as an index of sclerosis. We evaluated both atherosis and sclerosis of the thoracic aorta with transesophageal echocardiography (TEE) and examined the risk factors for both components of atherosclerosis.
METHODS Patient population. The subjects of this study were 100 consecutive patients in whom TEE was performed between July 1990 and January 1992. TEE examinations were performed in 48 patients who were awake and in 52 others who were under anesthesia for cardiovascular surgery. Two patients were excluded from the study or from data analysis for the following reasons: (1) the transesophageal probe could not be advanced because of esophageal stenosis, and (2) 10 patients were studied twice (the second data set was excluded in each case). Therefore the remaining 88 patients (62 men and 26 women; 46 awake patients and 42 patients undergoing cardiac surgery) aged 23 to 76 years (mean age, 59.7 + 12.6 years) constituted the database for this report. None of the patients had familial hypercholesterolemia. The clinical diagnoses of the awake patients were as follows: suspected left atria1 thrombus (n = 20), cerebral infarction (n = lo), transient ischemic attacks (n = 8), prostheticvalve (n = 4), ischemic heart disease (n = 2), and dilated cardiomyopathy (n = 2). In the patients undergoing cardiac surgery, the diagnoses were ischemic heart disease with coronary artery bypass grafting (n = 26), mitral valve disease with mitral valve replacement (n = 7) or open mitral commissurotomy (n = 2), aortic valve disease with aortic valve replacement (n = 3), atria1 septal defect with patch closure (n = 2), and abdominal aortic aneurysm with reconstruction (n = 2). Patients with thoracic aortic aneurysms or thoracic aortic dissection were excluded because the grade of atherosis could be overestimated when wall thickness was measured by TEE if there was mural thrombus or a thrombosed false lumen. All of the patients were given a standardized questionnaire, which evaluated the history of hypertension and diabetes mellitus and their smoking habits. Informed consent for participation was obtained from each patient. TEE. The transesophageal probe used in this study was a Toshiba PEF-511 SA (Toshiba Corp., Tokyo, Japan), equipped with a 5 MHz phased-array transducer with an axial resolution of less than 0.6 mm at the tip. This probe was connected to a Toshiba SSH-160 A ultrasound system. The awake patients fasted for at least 4 hours before examination. After pharyngeal anesthesia was induced with lidocaine spray and viscous lidocaine solution, the transesophageal probe was inserted into the esophagus
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with the patients lying in a supine and slightly lateral position. In patients undergoing cardiovascular surgery, the transesophageal probe was inserted into the esophagus in the supine position after induction of anesthesia and intubation. The scope was manipulated to obtain the short-axis view of the aorta, and the probe was moved up and down in the esophagus to image various planes of the aorta, from the ascending aorta to the descending aorta (about 20 cm under the arch). Blood pressure, heart rate, and ECG were also monitored. We assessed atherosis from the grade of atheroma in the thoracic aorta and sclerosis on the basis of arterial distensibility. TEE measurements for both these components of atherosclerosis were made simultaneously. Measurement of atherosis. In the aortic arch (segment 2), the thickness of the intima-media complex as defined by Pignoli4 and Pignoli et a1.5 was measured as the distance between the lumen-intima interface and the media-adventitia interface on B-mode images at the most distant position from the probe (anterior wall). The maximum thickness of the intima-media complex of this segment was recorded. The gain setting was kept as low as possible to prevent artificial overestimation of the thickness of the intima-media complex. The same measurements were performed in the descending aorta, which was divided into four segments of 5 cm in length according to the graduations on the transesophageal probe (segments 3 to 6). Finally, measurements were performed in the ascending aorta from 5 cm to 10 cm under the arch (segment 1) (Fig. 1). We manipulated the probe to bring in the maximum thickness of the intima-media complex within each segment (5 cm intervals). The probe was graduated in centimeters. Because of the interposition of the trachea between the esophagus and the ascending aorta, that portion of the ascending aorta immediately below the arch was excluded because it cannot be seen by transesophageal approach. The mean value of the maximum thickness of the intimamedia complex in the six segments of the thoracic aorta (MIMC) was used as an index of atherosis. Measurement of sclerosis. We used the stiffness parameter /3 (/3), which was defined by Hayashi et a1.s 7 as an index of sclerosis. /3 represents the stiffness of the vascular walls, which is independent of arterial pressure.s At the level of about 15 cm under the arch devoid of protruding atherosclerotic plaque, the changes of aortic dimensions during a cardiac cycle were recorded on M-mode (Fig. 2), and fl was calculated by the following formula: fi = In (Ps/ Pd) x Dd/(Ds - Dd), where In is natural logarithm, Ps is the systolic arterial pressure, Pd is the diastolic arterial pressure, Ds is the aortic dimension at systole, and Dd is the aortic dimension at diastole. Echocardiographic tracings were regarded as adequate for analysis whenever a continuous line of the anterior aortic wall endocardium could be visualized for at least five cardiac cycles, and adequate tracings were obtained in all examined patients whenever the procedure was attempted. The gain was set as low as possible to ensure detection of the actual anterior echo interface and the posterior lateral wall of the aorta by avoiding an artifactual decrease in aortic dimensions.
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Fig. 1. Measurement of morphologic atherosclerotic change of thoracic aorta. Mean value of maximum thickness of intima-media complex in six segmentsof thoracic aorta (MIMC) wascalculated. NC, Thicknessof intima-media complex; MIMC, (max IMC of segment 1 + max IMC of segment2 + max IMC of segment (3 + max IMC of segment4 + max IMC of segment5 + max IMC of segment6) divided by 6. Reproducibility. Tracings of 10 randomly selected patients were usedfor evaluation of the interobserver and intraobserver reproducibility. Intraobserver reproducibility was expressedas the SD divided by the average of the 10 measurements.The result was2.4% rt 0.5% for the MIMC value and 7.2% 2 1.3% for the value of /?. Interobserver reproducibility was 3.6% I 0.5% for MIMC and 9.3% -+ 2% for p. Repeatability. In 10 randomly selected patients, we performed two recordings in each patient and measured MIMC and p to evaluate the repeatability of the recordings. They were expressedasthe SD divided by the averageof the 10 measurements.The result was2.8% f 0.7% for the MIMC value, and 8.1% f 1.6% for the value of ,8. Risk factors. Ten risk factor variables were evaluated in all of the subjects. Information wasobtained from clinical history, physical examination, and blood test results. Age, gender, hyperlipidemia, diabetes mellitus, hypertension, obesity, and smoking were evaluated. Hyperlipidemia was evaluated from the low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levelsor the apolipoprotein A-I (apo A-I) and apolipoprotein B (apo B) levels. Blood sampleswere obtained from every patient after an overnight fast within 1 week before TEE examination. Total cholesterol, triglycerides, and HDL cholesterol were assayedenzymatically. The LDL choles-
terol level was computed with Friedwald’s formulag: LDL cholesterol = total cholesterol - HDL cholesterol - 0.2 x triglycerides. The apo A-I and apo B levels were measured by means of turbidimetric immunoassays(Daiichi Pure Chemical, Tokyo, Japan). If the patients were receiving medications for treatment of hyperlipidemia, blood sampling wasperformed at least 1 week after the suspensionof medication. Diabetes mellitus wasevaluated with the DM score,which was basedon the grade of diabetic retinopathy. The scorefor no diabetes mellitus was 0; simple diabetic retinopathy scored 1, preproliferative diabetic retinopathy scored 2, and proliferative diabetic retinopathy scored 3. Hypertension was evaluated with the World Health Organization classification.iO Obesity was evaluated from the body massindex, which was computed as weight (in kilograms)divided by height squared(in meters). Smoking was evaluated with Brinkman’s index’i (the number of cigarettessmokedper day x the number of years of smoking (Table I). Atherosis versus sclerosis. To evaluate the relationship between atherosis and sclerosisof the thoracic aorta, the MIMC and /3 values were compared by meansof simple linear correlation analysis. Baseline measurements. The thoracic aorta was removed from four human cadavers, which were different from the patient population, 3 to 7 hours after death. In a
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Fig. 2. Measurement of instantaneous dimensional diastole; Ds, dimension of aorta at systole.
trunk filled with a saline solution, the thickness of intimamedia complex of 11 sections of the aortas was measured. We removed the thoracic descending aorta with the esophagus and filled the aorta with a saline solution after we had clipped the end of the aorta and bound the branches. Then we clipped another end of the aorta while applying mild distending pressure and measured the thickness of intimamedia complex through the esophagus with TEE in the trunk. The 11 sections in which TEE examinations were performed were delimited by two metallic pins: these markers remained fixed in the specimen. After tissue fixation in 10% buffered formalin for 10 hours, the specimens were cut axially between two pins to evaluate the same segment that was imaged by TEE, and the segments were evaluated by microscopic pathologic examination. The thickness of the intima-media complex measured by TEE was compared with that measured by pathologic examination. Statistical analysis. To determine the major risk factors for atherosis and sclerosis of the thoracic aorta, potential risk factors for atherosclerosis were assessed by means of multivariate analysis. The dependent variables were MIMC and p, and the independent variables were age, gender, LDL cholesterol, HDL cholesterol, apo A-I, apo B, hypertension, diabetes mellitus, smoking, and obesity. The relationship between the thickness of the intima-media complex measured by TEE and that measured by pathologic examination and the relationship between MIMC and (3
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Table
I. Variables
aorta. Dd, Dimension
in multiple
regression
et al.
of aorta at
analysis
Dependent Variable MIMC (mean value of maximum thickness of intimamedia complex of 6 segments) @ (Stiffness parameter p) Independent variables Age Sex 0: Women 1: Men High-density lipoprotein cholesterol or apoiipoprotein Al Low-density lipoprotein cholesterol or apolipoprotein B Diabetes mellitus 0: 1: + no diabetic retinopathy 2: + simple diabetic retinopathy 3: + preproliferative diabetic retinopathy 4: + proliferative diabetic retinopathy Hypertension 0: 1: + WHO classification grade 1 2: + WHO classification grade 2 3: + WHO classification grade 3 Body mass index Weight (kg)/height squared (m2) Smoking Brinkman’s index = Cigarette consumption per day times the number of years smoked. WHO,
World
Health
Organization.
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II. Relation of risk factors to MIMC: regressionanalysis Table
/
-I
Factor
Age Gender HDL LDL DM HT BMI SM Multiple
Age Gender
1
1.5
2
2.5 IMC
3
3.5
4
APOA-I APOB DM HT BMI SM
4.5
by PE (mm)
Multiple
Fig. 3. Relationship between thickness of intima-media
complex (IMC) measuredby TEE and that measuredby pathologic examination (PE).
were examined with simple linear correlation; the maximum thickness of the intima-media complex of each segment wascompared with the maximum thickness of other segmentsby meansof Student’s t test, and p values <0.05 were consideredsignificant. RESULTS Baseline
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measurement. The thickness of the intima-media complex measured by TEE was compared with that measured by pathologic examination. Fig. 3 shows a close linear relationship between the thickness of the intima-media complex measured by TEE and that measured by pathologic examination (y = 0.92, x + 0.73, r = 0.99, p = O.OOOl), although the former values tended to be slightly higher than the latter. Two representative examples are presented in Fig. 4; one is a case of mild atherosclerosis and the other is severe atherosclerosis. The thickness of the intimamedia complex was clearly identified by TEE, as in the pathologic specimen (Elastica van-Gieson stain), and the two methods of assessment were in good agreement. Atherosis in each segment. In each segment the maximum thickness of the intima-media complex was measured, and the results (mean -t SD) were as follows: segment 1,1.3 -t 1.1 mm; segment 2,2.9 f 1.1 mm; segment 3, 1.6 + 1.0 mm; segment 4, 1.7 f 1.1 mm; segment 5, 1.7 f 0.9 mm; and segment 6, 1.7 & 1.2 mm. The value of segment 1 was significantly smaller than that of the other segments, and the value of segment 2 was significantly greater than that of the other segments (p < 0.05).
Multiple
SPRC
SEE
p Value
0.397
0.092 0.098 0.089 0.089 0.093 0.093 0.093 0.097
0.000 0.839 0.389 0.000
0.093
0.000
0.103 0.091 0.090 0.094 0.094 0.099 0.099
0.876 0.481 0.001 0.027 0.214 0.531
-0.020 -0.077 0.324
0.195 0.102 0.036
0.110
0.038 0.280 0.702 0.263
R* = 0.432 0.423 0.016 -0.065
0.297 0.212 0.117 0.063 0.137
0.169
R* = 0.432
MIMC,
Mean value of maximum thickness of i&ma-media complex in 6 of thoracic aotra; SPRC, standard partial regression coefficient: SEE, standard error of estimate; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; DM, diabetes mellitus; HT, hypertension; &VI, body mass index; SM, smoking; APOAI, apolipoprotein A-I; APOB, apolipoprotein B. segments
Risk factors for atherosis of the thoracic aorta. To determine the significant risk factors for atherosis of the thoracic aorta, multiple regression analysis was performed with MIMC as the dependent variable. This analysis indicated significant correlations with MIMC for age (p < O.OOl), LDL cholesterol (p < O.OOl), and diabetes mellitus (p < 0.05) (Table II); it was found that gender, HDL cholesterol, smoking (Brinkman’s index), and obesity were not significantly associated with MIMC. Similar results were obtained when apo A-I and apo B were introduced into the regression model instead of HDL cholesterol and LDL cholesterol, as shown in Table II (p = 0.001 for apo B). The distribution of DM score in the study population was as follows: 0 (n = 65), 1 (rz = lo), 2 (n = 6), 3 (n = 5), and 4 (n = 2). Risk factors for sclerosis of the thoracic aorta. The independent association between /3 (sclerosis index) and the risk factors for atherosclerosis was examined by multiple regression analysis (Table III). Age (p < 0.001) and hypertension (p = 0.001) were found to independently contribute to p, whereas no significant association was observed between @ and the other risk factors. Similar results were found when apo A-I and apo B were used instead of HDL cholesterol and LDL cholesterol (Table III). The distribution of hypertension scores in the study population was as follows: 0 (n = 57), 1 (n = 21), 2 (n = 6), and 3 (72= 4). Comparison between atherosis and sclerosis. The
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Fig. 4. Thickness of intima-media complex measuredby transesophagealechocadiography(left panel, 1 and 3) and that measuredby pathologic examination (right panel, 2 and 4). Upper panel (1,2), mild atherosclerotic section. Lower panel (3, and 4), severeatherosclerotic section. ZMC, Thickness of intimame-
dial complex.
correlation between MIMC and 0 was found to be weak but significant (y = 4.53, x + 2.94, r = 0.54, p = 0.0001) (Fig. 5).
.
DISCUSSION
In this study we observed atherosis (the grade of atheroma) and sclerosis (arterial distensibility) of the thoracic aorta by TEE and evaluated the risk factors for atherosis and sclerosis and the correlation between them. TEE is a useful method of evaluating thoracic aortic atherosclerosis with an acceptably low degree of risk.i” TEE provides excellent images of the thoracic aorta and because of the closeness of the aorta to the echocardiographic sensor allows the use of a focused high-frequency transducer that produces better resolution and an improved signal-to-noise ratio. Furthermore, TEE is superior to computed tomography, magnetic resonance imaging, or aortography for evaluating thoracic aortic atherosclerosis because both atherosis and sclerosis can be assessedsimultaneously. Atherosis was assessedas the mean value of the maximum thickness of the intima-media complex in the six segments of the thoracic aorta (MIMC) in this study. To evaluate carotid atherosclerosis, some investigators have used the thickness of the intima-
0: 0.5
,
, 1
,
I 1.5
.
, 2
,
, 2.5
MIMC
,
, 3
. 3.5
1 4
-
1 4.5
bnml
Fig. 5. Comparisonbetween MIMC and /3.
media complex as determined by ultrasonograd-v. i3-16Pignoli,4 Pignoli et a1.,5and Handa et a1.r3 have report&hat the thickness of the intima-media complex on carotid ultrasonography was correlated
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III. Relation of risk factors to @Multiple regression analysis Table
Factor
Age Gender HDL LDL DM HT BMI SM Multiple
Age Gender APOAl APOB DM HT BMI SM Multiple
SPRC
SEE
p Value
0.398 0.184 -0.063 0.063 0.051 0.335 -0.061 -0.026 R2 = 0.404
0.093 0.099 0.090 0.090 0.094 0.095 0.095 0.099
0.000 0.067 0.484 0.484 0.586 0.001 0.520 0.794
0.412 0.191 0.058 0.155 0.058 0.332 -0.042 -0.036 R2 = 0.412
0.094 0.104 0.092 0.090 0.095 0.094 0.100 0.099
0.000 0.069 0.528 0.090 0.542 0.001 0.675 0.717
@, Stiffness parameter@; SPRC, standard partial regression coefficient; SEE, standard error of estimate; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; DM, diabetes mellitus; HT, hypertension; BMI, body mass index; SM, smoking; APOAI, apolipoprotein A-l; APOB, apolipoprotein B.
significantly with that measured by pathologic examinations. In our pathologic study, we also obtained similar results from TEE of the thoracic aorta. To accurately determine the thickness by TEE, we measured only the most distant point of the thoracic aorta from the transesophageal probe; that is, we used only the range resolution of TEE and not the azimuth resolution. Thus the thickness of the intimamedia complex measured by TEE could be applied to clinical evaluation of atheroma of the thoracic aorta, and it has already been used in evaluating carotid lesions.13-i6However, the thickness of the intima-media complex measured by TEE tended to be slightly greater than that determined by pathologic examination. This discrepancy was attributed to the difficulty of discriminating the adventitia from the perivascular connective tissue on TEE and to the artifacts introduced during tissue processing for histologic evaluation, such as tissue shrinkage during formalin fixation. The plaque score, which is computed by summation of the plaque thicknesses in the thoracic aorta, is considered to be another good method of assessing atherosclerosis, and it has frequently been used in evaluating carotid lesions.3-‘6 However, lesions in only part of the artery are assessedwith the plaque score method. Accordingly, we increased the length of segment for investigation (5 cm) and the
February 1994 Heart Journal
mean value of the maximum thickness of the intimamedia complex in the six segments measured as an index for the entire length of the thoracic aorta (Fig. 1). We consider the MIMC to be a useful index of atherosis of the thoracic aorta because it is representative of not only localized marked atherosclerotic lesions but also of nonsignificant lesions, thereby offering an evaluation of the total thoracic aorta. Sclerosis was assessedwith the stiffness constant p. Hayashi et al. 6 ’ have studied the mechanical behavior of isolated human arteries with an optical technique with which they measured the change in external radius caused by distending pressure. They observed a linear relationship between the logarithm of relative pressure and the distension ratio. The slope of this exponential function is called 0, an index that characterizes, independently of pressure, the entire deformation behavior of the vascular wall within the physiologic pressure range. Using this index, some investigators8* 17+l8 have evaluated the degree of arterial sclerosis in the carotid artery and the abdominal aorta by ultrasonography. However, there were no attempts to evaluate sclerosis in the thoracic aorta with 0 until the development of TEE because it is difficult to investigate this part of the aorta by transthoracic echocardiography. However, TEE allows the determination of /3, and Pasierski et al.‘e have already reported a clinical study of thoracic aortic distensibility in which this parameter was used. We examined the risk factors for thoracic aortic atherosclerosis, which was divided into atherosis and sclerosis by multivariate analysis in this study, and found that age had the strongest association with both components of atherosclerosis. Except for age, LDL cholesterol (or apo B) and diabetes mellitus were independent predictors of the presence of atherosis of the thoracic aorta. In a pathologic study Sumiyoshi and Kurozumi20 have also showed that hyperlipidemia accelerates the aortic intimal thickening in Japanese individuals. Although apolipoproteins have been reported to be more strongly associated with coronary atherosclerosis than lipoproteins21 our data suggest that apo B and LDL cholesterol show a similar pattern of association with thoracic aortic lesions. Apolipoproteins do not seem to improve the predictive value of atherosis. As for diabetes mellitus, Crouse et a1.16showed a positive correlation between diabetes mellitus and carotid atherosclerosis evaluated by ultrasonography in univariate analysis, but this relationship disappeared when multivariate analysis was performed. However,
Volume 127, Number 2 American Heart Journal
our data and that of Davila-Roman et al.22 showed that diabetes mellitus was an independent predictor of the presence of atherosclerosis of the thoracic aorta by ultrasonographic evaluation. Therefore diabetes mellitus may be more strongly associated with thoracic aortic atherosclerosis than with carotid atherosclerosis. We believe that diabetes mellitus is an independent risk factor for atherosis of the thoracic aorta in the Japanese population. Although it is appropriate to evaluate the severity of diabetes mellitus according to the duration of disease, it is difficult to obtain accurate information on the length of a history of diabetes from a standardized questionnaire. Balodimos et a1.23and Shanzlin et a1.24reported that the duration of diabetes mellitus was closely correlated with the severity of diabetic retinopathy, so we also have used the DM score as an index of the severity of diabetic retinopathy to evaluate the severity of the disease. Besides age, the other significant risk factor for sclerosis of the thoracic aorta in the present study was hypertension. Imura et a1.r’ have shown that atherosclerotic change of the abdominal aorta, which was evaluated with p, was associated with hypertension in an autopsy study in the Japanese. There are many reports that cigarette smoking in Caucasians is associated with the development of lesions in the coronary, carotid, peripheral arteries, and in the aorta. In particular, Strong and Richards25 have reported that the effect of smoking on aortic atherosclerosis was more striking than that on coronary atherosclerosis. However, the relationship of smoking to atherosclerosis in the Japanese population is not well established. Our study showed that cigarette smoking was not significantly associated with thoracic aortic atherosclerosis, and Handa et al.13 have also reported no significant difference in the prevalence of carotid atherosclerosis between Japanese smokers and nonsmokers. This difference in the effect of smoking may perhaps be related to racial variations. Of all known risk factors, age has the strongest association wit,h atherosclerosis, particularly that of the thoracic aorta, as the present study confirmed. Our study indicated that the significant acquired risk factors for atherosis of the thoracic aorta are different from those for sclerosis because the former risk factors are LDL cholesterol (apo B) and diabetes mellitus, whereas the latter is hypertension. This may help to explain why the correlation between atherosis and sclerosis in the thoracic aorta was weak (although significant). Matsuzaki et al.26 also reported that hyperlipidemia and hypertension are
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important risk factors for the development of thoracic aortic atherosclerosis detected with TEE, but they only evaluated morphologic and not functional changes of aortic stiffness. In assessing atherosclerosis, it is better to evaluate atherosis and sclerosis separately. Limitations. Because our subjects were selected from a group of patients who were referred for TEE to assess a variety of cardiovascular complaints and because about half of them were under anesthesia, our findings may not reflect the situation in a healthy population, However, because the MTMC and /3 values measured under both awake conditions and anesthesia in seven patients were almost identical, the influence of anesthesia may only be slight. To confirm our data, population-based studies should be done in the future. Conclusions. To our knowledge, this is the first clinical study to separately evaluate atherosis and sclerosis in the thoracic aorta with TEE and to examine the risk factors for both components of atherosclerosis. We concluded that among the acquired risk factors, LDL cholesterol (apo B) and diabetes mellitus are important for atherosis of the thoracic aorta, whereas hypertension influences the development of sclerosis. Both components of atherosclerosis were significantly although weakly related to each other. Therefore when thoracic aortic atherosclerosis is assessed, both atherosis and sclerosis should be evaluated. TEE is a useful method for this purpose because both atherosis and sclerosis can be examined simultaneously. Because atherosclerosis plays a major role in the development of aortic aneurysms,r should carefully follow up elderly patients with high MIMC or 8 scores for the thoracic aorta and any of the above-mentioned risk factors. We thank Dr. S. Hasegawa and Dr. T. Ito for their kind cooperation in performing the TEE studies and Dr. J. Tanouchi for his invaluable advice. REFERENCES 1.
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Kahl FR, McMahan MR, Harpold GH. Risk factors For extracranial carotid artery atherosclerosis. Stroke 1987; 18990-6. Kawasaki K, Sasayama S, Yagi S, Asakawa T, Hirai ‘T. Noninvasive assessment of the age related changes in stiffness in major branches of the human arteries. Cardiovasc Res 1987; 21:678-87. Imura T, Yamamoto K, Satoh T, Mikami T, Yasuda H. Arteriosclerotic changes in the human abdominal aorta in vivo in relation to coronary heart disease and risk factors. Atherosclerosis 1988;73:149-55. Pasierski TJ, Binkley PF, Pearson AC. Evaluation of aortic distensibility with transesophageal echocardiography. AM HEART J 1992;123:12&3-92. Sumiyoshi A, Kurozumi T. Atherosclerosis in the pediatric age with special reference to initiation, progression and regression of atherosclerotic lesions. Jpn Circ J 1980;44:39-45. Avogaro P, Bittolo Bon G, Cazzolato G, Quinci GB. Are lipoproteins better discriminators than lipids for atherosclerosis? Lancet 1979;1:901-3. Davila-Roman VG, Barzilai B, Wareing TH, Murphy SF, Kouchoukos NT. Intraoperative ultrasonographic evaluation of the ascending aorta in 100 consecutive patients undergoing cardiac surgery. Circulation 1991;84(suppl III):III-47-111-53. Balodimos MC, Aiello LM, Gleason RE, Marble A. Retinonathy in mild diabetes. Arch Ophthal 1969;81:660-6. Shanzlin DJ. Jav WH. Fritz KJ. Trinathi RC. Gonen B. Hemoglobin Ai and diabetic retinopathy. Am J Ophthal 1979;8&1032-8. Strong JP, Richards ML. Cigarette smoking and atherosclerosis in autopsied men. Atherosclerosis 19’76;23:451-76. Matsuzaki M, Ono S, Tomochika Y, Michisige H, Tanaka N, Okuda F, Kusukawa R. Advances in transesophageal echocardiography for the evaluation of atherosclerosis lesions in thoracic aorta: the effects of hypertension, hypercholesterolemia, and aging on atherosclerotic lesions. Jpn Circ J 1992;56:590602.
degeneration and vessel stiffness and introduced the term atherosclerosis to indicate this combination.2 Blankenhorn and Kramsch3 reported that further studies of atherosclerosis should use a combination of measures to evaluate both atherosis and sclerosis. Atherosis represents the grade of atheroma morphologically, and sclerosis represents functional changes in arterial stiffness. In this study we measured the thickness of the intima-media complex4T 5 as an index of atherosis and determined the stiffness parameter @I 7 as an index of sclerosis. We evaluated both atherosis and sclerosis of the thoracic aorta with transesophageal echocardiography (TEE) and examined the risk factors for both components of atherosclerosis.
METHODS Patient population. The subjects of this study were 100 consecutive patients in whom TEE was performed between July 1990 and January 1992. TEE examinations were performed in 48 patients who were awake and in 52 others who were under anesthesia for cardiovascular surgery. Two patients were excluded from the study or from data analysis for the following reasons: (1) the transesophageal probe could not be advanced because of esophageal stenosis, and (2) 10 patients were studied twice (the second data set was excluded in each case). Therefore the remaining 88 patients (62 men and 26 women; 46 awake patients and 42 patients undergoing cardiac surgery) aged 23 to 76 years (mean age, 59.7 + 12.6 years) constituted the database for this report. None of the patients had familial hypercholesterolemia. The clinical diagnoses of the awake patients were as follows: suspected left atria1 thrombus (n = 20), cerebral infarction (n = lo), transient ischemic attacks (n = 8), prostheticvalve (n = 4), ischemic heart disease (n = 2), and dilated cardiomyopathy (n = 2). In the patients undergoing cardiac surgery, the diagnoses were ischemic heart disease with coronary artery bypass grafting (n = 26), mitral valve disease with mitral valve replacement (n = 7) or open mitral commissurotomy (n = 2), aortic valve disease with aortic valve replacement (n = 3), atria1 septal defect with patch closure (n = 2), and abdominal aortic aneurysm with reconstruction (n = 2). Patients with thoracic aortic aneurysms or thoracic aortic dissection were excluded because the grade of atherosis could be overestimated when wall thickness was measured by TEE if there was mural thrombus or a thrombosed false lumen. All of the patients were given a standardized questionnaire, which evaluated the history of hypertension and diabetes mellitus and their smoking habits. Informed consent for participation was obtained from each patient. TEE. The transesophageal probe used in this study was a Toshiba PEF-511 SA (Toshiba Corp., Tokyo, Japan), equipped with a 5 MHz phased-array transducer with an axial resolution of less than 0.6 mm at the tip. This probe was connected to a Toshiba SSH-160 A ultrasound system. The awake patients fasted for at least 4 hours before examination. After pharyngeal anesthesia was induced with lidocaine spray and viscous lidocaine solution, the transesophageal probe was inserted into the esophagus
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with the patients lying in a supine and slightly lateral position. In patients undergoing cardiovascular surgery, the transesophageal probe was inserted into the esophagus in the supine position after induction of anesthesia and intubation. The scope was manipulated to obtain the short-axis view of the aorta, and the probe was moved up and down in the esophagus to image various planes of the aorta, from the ascending aorta to the descending aorta (about 20 cm under the arch). Blood pressure, heart rate, and ECG were also monitored. We assessed atherosis from the grade of atheroma in the thoracic aorta and sclerosis on the basis of arterial distensibility. TEE measurements for both these components of atherosclerosis were made simultaneously. Measurement of atherosis. In the aortic arch (segment 2), the thickness of the intima-media complex as defined by Pignoli4 and Pignoli et a1.5 was measured as the distance between the lumen-intima interface and the media-adventitia interface on B-mode images at the most distant position from the probe (anterior wall). The maximum thickness of the intima-media complex of this segment was recorded. The gain setting was kept as low as possible to prevent artificial overestimation of the thickness of the intima-media complex. The same measurements were performed in the descending aorta, which was divided into four segments of 5 cm in length according to the graduations on the transesophageal probe (segments 3 to 6). Finally, measurements were performed in the ascending aorta from 5 cm to 10 cm under the arch (segment 1) (Fig. 1). We manipulated the probe to bring in the maximum thickness of the intima-media complex within each segment (5 cm intervals). The probe was graduated in centimeters. Because of the interposition of the trachea between the esophagus and the ascending aorta, that portion of the ascending aorta immediately below the arch was excluded because it cannot be seen by transesophageal approach. The mean value of the maximum thickness of the intimamedia complex in the six segments of the thoracic aorta (MIMC) was used as an index of atherosis. Measurement of sclerosis. We used the stiffness parameter /3 (/3), which was defined by Hayashi et a1.s 7 as an index of sclerosis. /3 represents the stiffness of the vascular walls, which is independent of arterial pressure.s At the level of about 15 cm under the arch devoid of protruding atherosclerotic plaque, the changes of aortic dimensions during a cardiac cycle were recorded on M-mode (Fig. 2), and fl was calculated by the following formula: fi = In (Ps/ Pd) x Dd/(Ds - Dd), where In is natural logarithm, Ps is the systolic arterial pressure, Pd is the diastolic arterial pressure, Ds is the aortic dimension at systole, and Dd is the aortic dimension at diastole. Echocardiographic tracings were regarded as adequate for analysis whenever a continuous line of the anterior aortic wall endocardium could be visualized for at least five cardiac cycles, and adequate tracings were obtained in all examined patients whenever the procedure was attempted. The gain was set as low as possible to ensure detection of the actual anterior echo interface and the posterior lateral wall of the aorta by avoiding an artifactual decrease in aortic dimensions.
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Fig. 1. Measurement of morphologic atherosclerotic change of thoracic aorta. Mean value of maximum thickness of intima-media complex in six segmentsof thoracic aorta (MIMC) wascalculated. NC, Thicknessof intima-media complex; MIMC, (max IMC of segment 1 + max IMC of segment2 + max IMC of segment (3 + max IMC of segment4 + max IMC of segment5 + max IMC of segment6) divided by 6. Reproducibility. Tracings of 10 randomly selected patients were usedfor evaluation of the interobserver and intraobserver reproducibility. Intraobserver reproducibility was expressedas the SD divided by the average of the 10 measurements.The result was2.4% rt 0.5% for the MIMC value and 7.2% 2 1.3% for the value of /?. Interobserver reproducibility was 3.6% I 0.5% for MIMC and 9.3% -+ 2% for p. Repeatability. In 10 randomly selected patients, we performed two recordings in each patient and measured MIMC and p to evaluate the repeatability of the recordings. They were expressedasthe SD divided by the averageof the 10 measurements.The result was2.8% f 0.7% for the MIMC value, and 8.1% f 1.6% for the value of ,8. Risk factors. Ten risk factor variables were evaluated in all of the subjects. Information wasobtained from clinical history, physical examination, and blood test results. Age, gender, hyperlipidemia, diabetes mellitus, hypertension, obesity, and smoking were evaluated. Hyperlipidemia was evaluated from the low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levelsor the apolipoprotein A-I (apo A-I) and apolipoprotein B (apo B) levels. Blood sampleswere obtained from every patient after an overnight fast within 1 week before TEE examination. Total cholesterol, triglycerides, and HDL cholesterol were assayedenzymatically. The LDL choles-
terol level was computed with Friedwald’s formulag: LDL cholesterol = total cholesterol - HDL cholesterol - 0.2 x triglycerides. The apo A-I and apo B levels were measured by means of turbidimetric immunoassays(Daiichi Pure Chemical, Tokyo, Japan). If the patients were receiving medications for treatment of hyperlipidemia, blood sampling wasperformed at least 1 week after the suspensionof medication. Diabetes mellitus wasevaluated with the DM score,which was basedon the grade of diabetic retinopathy. The scorefor no diabetes mellitus was 0; simple diabetic retinopathy scored 1, preproliferative diabetic retinopathy scored 2, and proliferative diabetic retinopathy scored 3. Hypertension was evaluated with the World Health Organization classification.iO Obesity was evaluated from the body massindex, which was computed as weight (in kilograms)divided by height squared(in meters). Smoking was evaluated with Brinkman’s index’i (the number of cigarettessmokedper day x the number of years of smoking (Table I). Atherosis versus sclerosis. To evaluate the relationship between atherosis and sclerosisof the thoracic aorta, the MIMC and /3 values were compared by meansof simple linear correlation analysis. Baseline measurements. The thoracic aorta was removed from four human cadavers, which were different from the patient population, 3 to 7 hours after death. In a
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Fig. 2. Measurement of instantaneous dimensional diastole; Ds, dimension of aorta at systole.
trunk filled with a saline solution, the thickness of intimamedia complex of 11 sections of the aortas was measured. We removed the thoracic descending aorta with the esophagus and filled the aorta with a saline solution after we had clipped the end of the aorta and bound the branches. Then we clipped another end of the aorta while applying mild distending pressure and measured the thickness of intimamedia complex through the esophagus with TEE in the trunk. The 11 sections in which TEE examinations were performed were delimited by two metallic pins: these markers remained fixed in the specimen. After tissue fixation in 10% buffered formalin for 10 hours, the specimens were cut axially between two pins to evaluate the same segment that was imaged by TEE, and the segments were evaluated by microscopic pathologic examination. The thickness of the intima-media complex measured by TEE was compared with that measured by pathologic examination. Statistical analysis. To determine the major risk factors for atherosis and sclerosis of the thoracic aorta, potential risk factors for atherosclerosis were assessed by means of multivariate analysis. The dependent variables were MIMC and p, and the independent variables were age, gender, LDL cholesterol, HDL cholesterol, apo A-I, apo B, hypertension, diabetes mellitus, smoking, and obesity. The relationship between the thickness of the intima-media complex measured by TEE and that measured by pathologic examination and the relationship between MIMC and (3
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Table
I. Variables
aorta. Dd, Dimension
in multiple
regression
et al.
of aorta at
analysis
Dependent Variable MIMC (mean value of maximum thickness of intimamedia complex of 6 segments) @ (Stiffness parameter p) Independent variables Age Sex 0: Women 1: Men High-density lipoprotein cholesterol or apoiipoprotein Al Low-density lipoprotein cholesterol or apolipoprotein B Diabetes mellitus 0: 1: + no diabetic retinopathy 2: + simple diabetic retinopathy 3: + preproliferative diabetic retinopathy 4: + proliferative diabetic retinopathy Hypertension 0: 1: + WHO classification grade 1 2: + WHO classification grade 2 3: + WHO classification grade 3 Body mass index Weight (kg)/height squared (m2) Smoking Brinkman’s index = Cigarette consumption per day times the number of years smoked. WHO,
World
Health
Organization.
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II. Relation of risk factors to MIMC: regressionanalysis Table
/
-I
Factor
Age Gender HDL LDL DM HT BMI SM Multiple
Age Gender
1
1.5
2
2.5 IMC
3
3.5
4
APOA-I APOB DM HT BMI SM
4.5
by PE (mm)
Multiple
Fig. 3. Relationship between thickness of intima-media
complex (IMC) measuredby TEE and that measuredby pathologic examination (PE).
were examined with simple linear correlation; the maximum thickness of the intima-media complex of each segment wascompared with the maximum thickness of other segmentsby meansof Student’s t test, and p values <0.05 were consideredsignificant. RESULTS Baseline
February 1994 Heart Journal
American
measurement. The thickness of the intima-media complex measured by TEE was compared with that measured by pathologic examination. Fig. 3 shows a close linear relationship between the thickness of the intima-media complex measured by TEE and that measured by pathologic examination (y = 0.92, x + 0.73, r = 0.99, p = O.OOOl), although the former values tended to be slightly higher than the latter. Two representative examples are presented in Fig. 4; one is a case of mild atherosclerosis and the other is severe atherosclerosis. The thickness of the intimamedia complex was clearly identified by TEE, as in the pathologic specimen (Elastica van-Gieson stain), and the two methods of assessment were in good agreement. Atherosis in each segment. In each segment the maximum thickness of the intima-media complex was measured, and the results (mean -t SD) were as follows: segment 1,1.3 -t 1.1 mm; segment 2,2.9 f 1.1 mm; segment 3, 1.6 + 1.0 mm; segment 4, 1.7 f 1.1 mm; segment 5, 1.7 f 0.9 mm; and segment 6, 1.7 & 1.2 mm. The value of segment 1 was significantly smaller than that of the other segments, and the value of segment 2 was significantly greater than that of the other segments (p < 0.05).
Multiple
SPRC
SEE
p Value
0.397
0.092 0.098 0.089 0.089 0.093 0.093 0.093 0.097
0.000 0.839 0.389 0.000
0.093
0.000
0.103 0.091 0.090 0.094 0.094 0.099 0.099
0.876 0.481 0.001 0.027 0.214 0.531
-0.020 -0.077 0.324
0.195 0.102 0.036
0.110
0.038 0.280 0.702 0.263
R* = 0.432 0.423 0.016 -0.065
0.297 0.212 0.117 0.063 0.137
0.169
R* = 0.432
MIMC,
Mean value of maximum thickness of i&ma-media complex in 6 of thoracic aotra; SPRC, standard partial regression coefficient: SEE, standard error of estimate; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; DM, diabetes mellitus; HT, hypertension; &VI, body mass index; SM, smoking; APOAI, apolipoprotein A-I; APOB, apolipoprotein B. segments
Risk factors for atherosis of the thoracic aorta. To determine the significant risk factors for atherosis of the thoracic aorta, multiple regression analysis was performed with MIMC as the dependent variable. This analysis indicated significant correlations with MIMC for age (p < O.OOl), LDL cholesterol (p < O.OOl), and diabetes mellitus (p < 0.05) (Table II); it was found that gender, HDL cholesterol, smoking (Brinkman’s index), and obesity were not significantly associated with MIMC. Similar results were obtained when apo A-I and apo B were introduced into the regression model instead of HDL cholesterol and LDL cholesterol, as shown in Table II (p = 0.001 for apo B). The distribution of DM score in the study population was as follows: 0 (n = 65), 1 (rz = lo), 2 (n = 6), 3 (n = 5), and 4 (n = 2). Risk factors for sclerosis of the thoracic aorta. The independent association between /3 (sclerosis index) and the risk factors for atherosclerosis was examined by multiple regression analysis (Table III). Age (p < 0.001) and hypertension (p = 0.001) were found to independently contribute to p, whereas no significant association was observed between @ and the other risk factors. Similar results were found when apo A-I and apo B were used instead of HDL cholesterol and LDL cholesterol (Table III). The distribution of hypertension scores in the study population was as follows: 0 (n = 57), 1 (n = 21), 2 (n = 6), and 3 (72= 4). Comparison between atherosis and sclerosis. The
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Fig. 4. Thickness of intima-media complex measuredby transesophagealechocadiography(left panel, 1 and 3) and that measuredby pathologic examination (right panel, 2 and 4). Upper panel (1,2), mild atherosclerotic section. Lower panel (3, and 4), severeatherosclerotic section. ZMC, Thickness of intimame-
dial complex.
correlation between MIMC and 0 was found to be weak but significant (y = 4.53, x + 2.94, r = 0.54, p = 0.0001) (Fig. 5).
.
DISCUSSION
In this study we observed atherosis (the grade of atheroma) and sclerosis (arterial distensibility) of the thoracic aorta by TEE and evaluated the risk factors for atherosis and sclerosis and the correlation between them. TEE is a useful method of evaluating thoracic aortic atherosclerosis with an acceptably low degree of risk.i” TEE provides excellent images of the thoracic aorta and because of the closeness of the aorta to the echocardiographic sensor allows the use of a focused high-frequency transducer that produces better resolution and an improved signal-to-noise ratio. Furthermore, TEE is superior to computed tomography, magnetic resonance imaging, or aortography for evaluating thoracic aortic atherosclerosis because both atherosis and sclerosis can be assessedsimultaneously. Atherosis was assessedas the mean value of the maximum thickness of the intima-media complex in the six segments of the thoracic aorta (MIMC) in this study. To evaluate carotid atherosclerosis, some investigators have used the thickness of the intima-
0: 0.5
,
, 1
,
I 1.5
.
, 2
,
, 2.5
MIMC
,
, 3
. 3.5
1 4
-
1 4.5
bnml
Fig. 5. Comparisonbetween MIMC and /3.
media complex as determined by ultrasonograd-v. i3-16Pignoli,4 Pignoli et a1.,5and Handa et a1.r3 have report&hat the thickness of the intima-media complex on carotid ultrasonography was correlated
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III. Relation of risk factors to @Multiple regression analysis Table
Factor
Age Gender HDL LDL DM HT BMI SM Multiple
Age Gender APOAl APOB DM HT BMI SM Multiple
SPRC
SEE
p Value
0.398 0.184 -0.063 0.063 0.051 0.335 -0.061 -0.026 R2 = 0.404
0.093 0.099 0.090 0.090 0.094 0.095 0.095 0.099
0.000 0.067 0.484 0.484 0.586 0.001 0.520 0.794
0.412 0.191 0.058 0.155 0.058 0.332 -0.042 -0.036 R2 = 0.412
0.094 0.104 0.092 0.090 0.095 0.094 0.100 0.099
0.000 0.069 0.528 0.090 0.542 0.001 0.675 0.717
@, Stiffness parameter@; SPRC, standard partial regression coefficient; SEE, standard error of estimate; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; DM, diabetes mellitus; HT, hypertension; BMI, body mass index; SM, smoking; APOAI, apolipoprotein A-l; APOB, apolipoprotein B.
significantly with that measured by pathologic examinations. In our pathologic study, we also obtained similar results from TEE of the thoracic aorta. To accurately determine the thickness by TEE, we measured only the most distant point of the thoracic aorta from the transesophageal probe; that is, we used only the range resolution of TEE and not the azimuth resolution. Thus the thickness of the intimamedia complex measured by TEE could be applied to clinical evaluation of atheroma of the thoracic aorta, and it has already been used in evaluating carotid lesions.13-i6However, the thickness of the intima-media complex measured by TEE tended to be slightly greater than that determined by pathologic examination. This discrepancy was attributed to the difficulty of discriminating the adventitia from the perivascular connective tissue on TEE and to the artifacts introduced during tissue processing for histologic evaluation, such as tissue shrinkage during formalin fixation. The plaque score, which is computed by summation of the plaque thicknesses in the thoracic aorta, is considered to be another good method of assessing atherosclerosis, and it has frequently been used in evaluating carotid lesions.3-‘6 However, lesions in only part of the artery are assessedwith the plaque score method. Accordingly, we increased the length of segment for investigation (5 cm) and the
February 1994 Heart Journal
mean value of the maximum thickness of the intimamedia complex in the six segments measured as an index for the entire length of the thoracic aorta (Fig. 1). We consider the MIMC to be a useful index of atherosis of the thoracic aorta because it is representative of not only localized marked atherosclerotic lesions but also of nonsignificant lesions, thereby offering an evaluation of the total thoracic aorta. Sclerosis was assessedwith the stiffness constant p. Hayashi et al. 6 ’ have studied the mechanical behavior of isolated human arteries with an optical technique with which they measured the change in external radius caused by distending pressure. They observed a linear relationship between the logarithm of relative pressure and the distension ratio. The slope of this exponential function is called 0, an index that characterizes, independently of pressure, the entire deformation behavior of the vascular wall within the physiologic pressure range. Using this index, some investigators8* 17+l8 have evaluated the degree of arterial sclerosis in the carotid artery and the abdominal aorta by ultrasonography. However, there were no attempts to evaluate sclerosis in the thoracic aorta with 0 until the development of TEE because it is difficult to investigate this part of the aorta by transthoracic echocardiography. However, TEE allows the determination of /3, and Pasierski et al.‘e have already reported a clinical study of thoracic aortic distensibility in which this parameter was used. We examined the risk factors for thoracic aortic atherosclerosis, which was divided into atherosis and sclerosis by multivariate analysis in this study, and found that age had the strongest association with both components of atherosclerosis. Except for age, LDL cholesterol (or apo B) and diabetes mellitus were independent predictors of the presence of atherosis of the thoracic aorta. In a pathologic study Sumiyoshi and Kurozumi20 have also showed that hyperlipidemia accelerates the aortic intimal thickening in Japanese individuals. Although apolipoproteins have been reported to be more strongly associated with coronary atherosclerosis than lipoproteins21 our data suggest that apo B and LDL cholesterol show a similar pattern of association with thoracic aortic lesions. Apolipoproteins do not seem to improve the predictive value of atherosis. As for diabetes mellitus, Crouse et a1.16showed a positive correlation between diabetes mellitus and carotid atherosclerosis evaluated by ultrasonography in univariate analysis, but this relationship disappeared when multivariate analysis was performed. However,
Volume 127, Number 2 American Heart Journal
our data and that of Davila-Roman et al.22 showed that diabetes mellitus was an independent predictor of the presence of atherosclerosis of the thoracic aorta by ultrasonographic evaluation. Therefore diabetes mellitus may be more strongly associated with thoracic aortic atherosclerosis than with carotid atherosclerosis. We believe that diabetes mellitus is an independent risk factor for atherosis of the thoracic aorta in the Japanese population. Although it is appropriate to evaluate the severity of diabetes mellitus according to the duration of disease, it is difficult to obtain accurate information on the length of a history of diabetes from a standardized questionnaire. Balodimos et a1.23and Shanzlin et a1.24reported that the duration of diabetes mellitus was closely correlated with the severity of diabetic retinopathy, so we also have used the DM score as an index of the severity of diabetic retinopathy to evaluate the severity of the disease. Besides age, the other significant risk factor for sclerosis of the thoracic aorta in the present study was hypertension. Imura et a1.r’ have shown that atherosclerotic change of the abdominal aorta, which was evaluated with p, was associated with hypertension in an autopsy study in the Japanese. There are many reports that cigarette smoking in Caucasians is associated with the development of lesions in the coronary, carotid, peripheral arteries, and in the aorta. In particular, Strong and Richards25 have reported that the effect of smoking on aortic atherosclerosis was more striking than that on coronary atherosclerosis. However, the relationship of smoking to atherosclerosis in the Japanese population is not well established. Our study showed that cigarette smoking was not significantly associated with thoracic aortic atherosclerosis, and Handa et al.13 have also reported no significant difference in the prevalence of carotid atherosclerosis between Japanese smokers and nonsmokers. This difference in the effect of smoking may perhaps be related to racial variations. Of all known risk factors, age has the strongest association wit,h atherosclerosis, particularly that of the thoracic aorta, as the present study confirmed. Our study indicated that the significant acquired risk factors for atherosis of the thoracic aorta are different from those for sclerosis because the former risk factors are LDL cholesterol (apo B) and diabetes mellitus, whereas the latter is hypertension. This may help to explain why the correlation between atherosis and sclerosis in the thoracic aorta was weak (although significant). Matsuzaki et al.26 also reported that hyperlipidemia and hypertension are
Nishino et al. 343
important risk factors for the development of thoracic aortic atherosclerosis detected with TEE, but they only evaluated morphologic and not functional changes of aortic stiffness. In assessing atherosclerosis, it is better to evaluate atherosis and sclerosis separately. Limitations. Because our subjects were selected from a group of patients who were referred for TEE to assess a variety of cardiovascular complaints and because about half of them were under anesthesia, our findings may not reflect the situation in a healthy population, However, because the MTMC and /3 values measured under both awake conditions and anesthesia in seven patients were almost identical, the influence of anesthesia may only be slight. To confirm our data, population-based studies should be done in the future. Conclusions. To our knowledge, this is the first clinical study to separately evaluate atherosis and sclerosis in the thoracic aorta with TEE and to examine the risk factors for both components of atherosclerosis. We concluded that among the acquired risk factors, LDL cholesterol (apo B) and diabetes mellitus are important for atherosis of the thoracic aorta, whereas hypertension influences the development of sclerosis. Both components of atherosclerosis were significantly although weakly related to each other. Therefore when thoracic aortic atherosclerosis is assessed, both atherosis and sclerosis should be evaluated. TEE is a useful method for this purpose because both atherosis and sclerosis can be examined simultaneously. Because atherosclerosis plays a major role in the development of aortic aneurysms,r should carefully follow up elderly patients with high MIMC or 8 scores for the thoracic aorta and any of the above-mentioned risk factors. We thank Dr. S. Hasegawa and Dr. T. Ito for their kind cooperation in performing the TEE studies and Dr. J. Tanouchi for his invaluable advice. REFERENCES 1.
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Kahl FR, McMahan MR, Harpold GH. Risk factors For extracranial carotid artery atherosclerosis. Stroke 1987; 18990-6. Kawasaki K, Sasayama S, Yagi S, Asakawa T, Hirai ‘T. Noninvasive assessment of the age related changes in stiffness in major branches of the human arteries. Cardiovasc Res 1987; 21:678-87. Imura T, Yamamoto K, Satoh T, Mikami T, Yasuda H. Arteriosclerotic changes in the human abdominal aorta in vivo in relation to coronary heart disease and risk factors. Atherosclerosis 1988;73:149-55. Pasierski TJ, Binkley PF, Pearson AC. Evaluation of aortic distensibility with transesophageal echocardiography. AM HEART J 1992;123:12&3-92. Sumiyoshi A, Kurozumi T. Atherosclerosis in the pediatric age with special reference to initiation, progression and regression of atherosclerotic lesions. Jpn Circ J 1980;44:39-45. Avogaro P, Bittolo Bon G, Cazzolato G, Quinci GB. Are lipoproteins better discriminators than lipids for atherosclerosis? Lancet 1979;1:901-3. Davila-Roman VG, Barzilai B, Wareing TH, Murphy SF, Kouchoukos NT. Intraoperative ultrasonographic evaluation of the ascending aorta in 100 consecutive patients undergoing cardiac surgery. Circulation 1991;84(suppl III):III-47-111-53. Balodimos MC, Aiello LM, Gleason RE, Marble A. Retinonathy in mild diabetes. Arch Ophthal 1969;81:660-6. Shanzlin DJ. Jav WH. Fritz KJ. Trinathi RC. Gonen B. Hemoglobin Ai and diabetic retinopathy. Am J Ophthal 1979;8&1032-8. Strong JP, Richards ML. Cigarette smoking and atherosclerosis in autopsied men. Atherosclerosis 19’76;23:451-76. Matsuzaki M, Ono S, Tomochika Y, Michisige H, Tanaka N, Okuda F, Kusukawa R. Advances in transesophageal echocardiography for the evaluation of atherosclerosis lesions in thoracic aorta: the effects of hypertension, hypercholesterolemia, and aging on atherosclerotic lesions. Jpn Circ J 1992;56:590602.